A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.
A family of DNA plant viruses that infect eukaryotic algae.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.
A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.
A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.
A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION.
Any chemical species which accepts an electron-pair from a LEWIS BASE in a chemical bonding reaction.
Chemicals with two conjoined aromatic rings incorporating two nitrogen atoms and one of the carbons oxidized with a keto oxygen.
Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Methods used for the chemical synthesis of compounds. Included under this heading are laboratory methods used to synthesize a variety of chemicals and drugs.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Scandium. An element of the rare earth family of metals. It has the atomic symbol Sc, atomic number 21, and atomic weight 45.
Compounds with a benzene ring fused to a thiazole ring.
Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed)
Flavoring agent and non-nutritive sweetener.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A subspecialty of pathology concerned with the molecular basis (e.g., mutations) of various diseases.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.
An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.
The transmission and reproduction of transient images of fixed or moving objects. An electronic system of transmitting such images together with sound over a wire or through space by apparatus that converts light and sound into electrical waves and reconverts them into visible light rays and audible sound. (From Webster, 3rd ed)
Recording of visual and sometimes sound signals on magnetic tape.
A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.
A measure of the total greenhouse gas emissions produced by an individual, organization, event, or product. It is measured in units of equivalent kilograms of CARBON DIOXIDE generated in a given time frame.
A nonmetallic element with atomic symbol C, atomic number 6, and atomic weight [12.0096; 12.0116]. It may occur as several different allotropes including DIAMOND; CHARCOAL; and GRAPHITE; and as SOOT from incompletely burned fuel.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)

Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme. (1/3696)

The ability of inhibitors selective for the type 5 phosphodiesterase isozyme (PDE5) to act on the photoreceptor PDE isozyme (PDE6, the central effector enzyme for visual transduction) is poorly understood. Because PDE5 inhibitors are currently used as therapeutic agents, it is important to assess the potency and mechanism of action of this class of PDE inhibitor on PDE6. We show that E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-ca rboxylate sesquihydrate) inhibits activated PDE6 (KI = 1.7 nM) as potently as PDE5. This makes E4021 the most potent inhibitor of PDE6 discovered to date. The effectiveness of E4021 to inhibit nonactivated PDE6 (with bound inhibitory gamma subunits) is reduced 40-fold compared with the activated enzyme. Furthermore, at intermediate E4021 concentrations and high cGMP concentrations, nonactivated PDE undergoes activation of cGMP hydrolysis rather than inhibition. We demonstrate direct competition of E4021 and the gamma subunits for binding to the catalytic site. Measurements of cGMP binding to noncatalytic regulatory sites on the catalytic subunits of PDE6 rule out an allosteric effect of E4021 by direct binding to these noncatalytic sites. We conclude that E4021 is a competitive inhibitor of cGMP hydrolysis and that the gamma subunit also competes with both E4021 and substrate for catalytic site binding. An understanding of the effects of PDE5-targeted drugs on retinal PDE6 requires a knowledge of the complex interactions among substrate, drug, and inhibitory gamma subunit at the catalytic site of both nonactivated and activated forms of PDE6.  (+info)

Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage. (2/3696)

DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are activated by DNA strand breaks and participate in DNA repair. We investigated the interactive effects of inhibitors of these enzymes [wortmannin (WM), which inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM) potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the cytotoxicity of temozolomide, and an additive effect on the DEF10 value was obtained with the combined inhibitors. Using the same inhibitor concentrations, their single and combined effects on DSB and SSB levels following IR were assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05, respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had an additive effect. WM had no effect on SSB levels, either alone or in combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025 compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the inhibitors on DSB levels showed that they were near maximal by 20 microM WM and 300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased net DSB levels over a 3 h time period; when they were combined, net DSB levels at 3 h were identical to DSB levels immediately post-IR. The combined use of DNA repair inhibitors may have therapeutic potential.  (+info)

A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. (3/3696)

2-Amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride (nolatrexed dihydrochloride, Thymitaq, AG337), a specific inhibitor of thymidylate synthase, was developed using protein structure-based drug design. Intravenously administered nolatrexed is active clinically. As oral bioavailability is high (70-100%), nolatrexed was administered orally, 6 hourly for 10 days, at 3-week intervals, and dose escalated from 80 to 572 mg m(-2) day(-1) in 23 patients. Common toxicity criteria (CTC) grade 3 toxicities included nausea, vomiting, stomatitis and liver function test (LFT) abnormalities. Thrombocytopenia (grade 1 or 2) occurred at doses > or = 318 mg m(-2) day(-1) and neutropenia (grade 2) at 429 and 572 mg m(-2) day(-1). An erythematous maculopapular rash occurred at dosages > or = 318 mg m(-2) day(-1) (7 out of 19 patients). LFT abnormalities occurred in two out of six patients (grade 3 or 4 bilirubin and grade 3 alanine transaminase) at 572 mg m(-2) day(-1). Nolatrexed plasma concentrations 1 h after dosing were 6-16 microg ml(-1), and trough 3-8 microg ml(-1), at 572 mg m(-2) day(-1). Inhibition of thymidylate synthase was demonstrated by elevation of plasma deoxyuridine. Six-hourly oral nolatrexed for 10 days was associated with antiproliferative effects, but nausea and vomiting was dose limiting at 572 mg m(-2) day(-1). Nine patients were treated at 429 mg m(-2) day(-1); three out of nine experienced grade 3 nausea, but 17 out of 22 treatment courses were completed (with the co-administration of prophylactic antiemetics) and this dose level could be considered for phase II testing.  (+info)

Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868. (4/3696)

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor alpha (TGF-alpha)-stimulated growth was completely inhibited by concentrations > or =0.3 microM in the PE01 and PE04 cell lines and by > or =0.1 microM in SKOV-3 cells. TGF-alpha inhibition of PE01CDDP growth was reversed by concentrations > or =0.1 microM ZM 252868. TGF-alpha-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations > or =0.3 microM, completely inhibited TGF-alpha-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 microM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.  (+info)

Keratinocyte collagenase-1 expression requires an epidermal growth factor receptor autocrine mechanism. (5/3696)

In response to cutaneous injury, expression of collagenase-1 is induced in keratinocytes via alpha2beta1 contact with native type I collagen, and enzyme activity is essential for cell migration over this substratum. However, the cellular mechanism(s) mediating integrin signaling remain poorly understood. We demonstrate here that treatment of keratinocytes cultured on type I collagen with epidermal growth factor receptor (EGFR) blocking antibodies or a specific receptor antagonist inhibited cell migration across type I collagen and the matrix-directed stimulation of collagenase-1 production. Additionally, stimulation of collagenase-1 expression by hepatocyte growth factor, transforming growth factor-beta1, and interferon-gamma was blocked by EGFR inhibitors, suggesting a required EGFR autocrine signaling step for enzyme expression. Collagenase-1 mRNA was not detectable in keratinocytes isolated immediately from normal skin, but increased progressively following 2 h of contact with collagen. In contrast, EGFR mRNA was expressed at high steady-state levels in keratinocytes isolated immediately from intact skin but was absent following 2 h cell contact with collagen, suggesting down-regulation following receptor activation. Indeed, tyrosine phosphorylation of the EGFR was evident as early as 10 min following cell contact with collagen. Treatment of keratinocytes cultured on collagen with EGFR antagonist or heparin-binding (HB)-EGF neutralizing antibodies dramatically inhibited the sustained expression (6-24 h) of collagenase-1 mRNA, whereas initial induction by collagen alone (2 h) was unaffected. Finally, expression of collagenase-1 in ex vivo wounded skin and re-epithelialization of partial thickness porcine burn wounds was blocked following treatment with EGFR inhibitors. These results demonstrate that keratinocyte contact with type I collagen is sufficient to induce collagenase-1 expression, whereas sustained enzyme production requires autocrine EGFR activation by HB-EGF as an obligatory intermediate step, thereby maintaining collagenase-1-dependent migration during the re-epithelialization of epidermal wounds.  (+info)

A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus. (6/3696)

Three lipophilic quinazoline-based aminomethyl pyridine compounds, which differ only in the position of the nitrogen in their pyridine ring, are described. CB300179 (2-pyridine), CB300189 (4-pyridine) and CB30865 (3-pyridine) all inhibited isolated mammalian TS with IC50 values of 508, 250 and 156 nM respectively. CB30865 was the most potent growth inhibitory agent (IC50 values in the range 1-100 nM for several mouse and human cell types). CB300179 and CB300189 were active in the micromolar range. Against W1L2 cells, CB300179 and CB300189 demonstrated reduced potency in the presence of exogenous thymidine (dThd), and against a W1L2:C1 TS overproducing cell line. In contrast, CB30865 retained activity in these systems. Furthermore, combinations of precursors and end products of folate metabolism, e.g. dThd/hypoxanthine (HX) or leucovorin (LV), did not prevent activity. CB30865 did not interfere with the incorporation of tritiated dThd, uridine or leucine after 4 h. A cell line was raised with acquired resistance to CB30865 (W1L2:R865; > 200-fold), which was not cross-resistant to CB300179 or CB300189. In addition, W1L2:R865 cells were as sensitive as parental cells to agents from all the major chemotherapeutic drug classes. CB300179 and CB300189 induced an S phase accumulation (preventable by co-administration of dThd). No cell cycle redistribution was observed following exposure (4-48 h) to an equitoxic concentration of CB30865. In the NCI anticancer drug-discovery screen, CB30865 displayed a pattern of activity which was not consistent with known anti-tumour agents. These data suggest that CB30865 represents a class of potent potential anti-tumour agents with a novel mechanism of action.  (+info)

Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy. (7/3696)

ErbB2 (HER2, Neu), a member of the epidermal growth factor (EGF) receptor tyrosine kinase family, is often overexpressed in breast cancer and other malignancies. ErbB2 homodimerizes but also presents as a common auxiliary subunit of the EGF and heregulin receptors (erbB1 or EGFR; and erbB3-4, respectively), with which it heteroassociates. ErbB2 is generally regarded as an orphan (ligand-less) receptor with a very potent kinase domain activated either via its associated partners or constitutively as a consequence of discrete mutations. It follows that the extent and regulation of its cell surface interactions are of central importance. We have studied the large-scale association pattern of erbB2 in quiescent and activated cells labeled with fluorescent anti-erbB2 monoclonal antibodies using scanning near-field optical microscopy (SNOM). ErbB2 was found to be concentrated in irregular membrane patches with a mean diameter of approx. 0.5 microm in nonactivated SKBR3 and MDA453 human breast tumor cells. The average number of erbB2 proteins in a single cluster on nonactivated SKBR3 cells was about 10(3). Activation of SKBR3 cells with EGF, heregulin as well as a partially agonistic anti-erbB2 monoclonal antibody led to an increase in the mean cluster diameter to 0.6-0.9 microm, irrespective of the ligand. The EGF-induced increase in the erbB2 cluster size was inhibited by the EGFR-specific tyrosine kinase inhibitor PD153035. The average size of erbB2 clusters on the erbB2-transfected line of CHO cells (CB2) was similar to that of activated SKBR3 cells, a finding correlated with the increased base-line tyrosine phosphorylation of erbB2 in cells expressing only erbB2. We conclude that an increase in cluster size may constitute a general phenomenon in the activation of erbB2.  (+info)

Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. Role of focal adhesions and receptor tyrosine kinases. (8/3696)

G protein-coupled receptors (GPCRs) initiate Ras-dependent activation of the Erk 1/2 mitogen-activated protein kinase cascade by stimulating recruitment of Ras guanine nucleotide exchange factors to the plasma membrane. Both integrin-based focal adhesion complexes and receptor tyrosine kinases have been proposed as scaffolds upon which the GPCR-induced Ras activation complex may assemble. Using specific inhibitors of focal adhesion complex assembly and receptor tyrosine kinase activation, we have determined the relative contribution of each to activation of the Erk 1/2 cascade following stimulation of endogenous GPCRs in three different cell types. The tetrapeptide RGDS, which inhibits integrin dimerization, and cytochalasin D, which depolymerizes the actin cytoskeleton, disrupt the assembly of focal adhesions. In PC12 rat pheochromocytoma cells, both agents block lysophosphatidic acid (LPA)- and bradykinin-stimulated Erk 1/2 phosphorylation, suggesting that intact focal adhesion complexes are required for GPCR-induced mitogen-activated protein kinase activation in these cells. In Rat 1 fibroblasts, Erk 1/2 activation via LPA and thrombin receptors is completely insensitive to both agents. Conversely, the epidermal growth factor receptor-specific tyrphostin AG1478 inhibits GPCR-mediated Erk 1/2 activation in Rat 1 cells but has no effect in PC12 cells. In HEK-293 human embryonic kidney cells, LPA and thrombin receptor-mediated Erk 1/2 activation is partially sensitive to both the RGDS peptide and tyrphostin AG1478, suggesting that both focal adhesion and receptor tyrosine kinase scaffolds are employed in these cells. The dependence of GPCR-mediated Erk 1/2 activation on intact focal adhesions correlates with expression of the calcium-regulated focal adhesion kinase, Pyk2. In all three cell types, GPCR-stimulated Erk 1/2 activation is significantly inhibited by the Src kinase inhibitors, herbimycin A and 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo-D-3,4-pyrimidine (PP1), suggesting that Src family nonreceptor tyrosine kinases represent a point of convergence for signals originating from either scaffold.  (+info)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently recommended by international guidelines as first-line treatment in patients with advanced EGFR-mutant non-small-cell lung cancer. With the availability of drugs, more and more patients choose EGFR-TKI treatment. However, pharmaceutical drugs used in clinical practice have side effects, such as diarrhea, paronychia, and hepatotoxicity. Mental or conscious disturbance has never been reported before. In our clinical center, we found that several patients with advanced lung adenocarcinoma developed a mental disorder or conscious disturbance after EGFR-TKI treatment. This situation has not previously been reported. We conducted a retrospective study of patients with advanced lung adenocarcinoma treated with EGFR-TKI who showed a mental disorder or conscious disturbance. We reported five cases of lung adenocarcinoma who developed a mental disorder or conscious disturbance after treatment with EGFR-TKI. The main ...
Chai, C.S. and Liam, C (2017) Resistance mechanisms causing first-line epidermal growth factor receptor-tyrosine kinase inhibitor treatment failure. Annals of Oncology, 28 (10). ISSN 1569-8041 ...
MOESM12 of STAT3 induces G9a to exacerbate HER3 expression for the survival of epidermal growth factor receptor-tyrosine kinase inhibitors in lung cancers
Title:Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity. VOLUME: 17 ISSUE: 6. Author(s):Marwa F. Ahmed* and Naja Magdy. Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Department of Pharmacology and toxicology, Faculty of Pharmacy, Taif University, Taif 26571. Keywords:Breast cancer, EGFR TK, IC50, quinazolines, synthesis, design.. Abstract:Background: Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity. Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and ...
TY - JOUR. T1 - Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with chemotherapy for advanced non-small-cell lung cancer. AU - Hightower, Mary. AU - Belani, Chandra P.. AU - Jain, Vinay K.. PY - 2003/5. Y1 - 2003/5. UR - http://www.scopus.com/inward/record.url?scp=0038080166&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0038080166&partnerID=8YFLogxK. U2 - 10.1016/S1525-7304(11)70302-3. DO - 10.1016/S1525-7304(11)70302-3. M3 - Article. C2 - 14599299. AN - SCOPUS:0038080166. VL - 4. SP - 336. EP - 338. JO - Clinical Lung Cancer. JF - Clinical Lung Cancer. SN - 1525-7304. IS - 6. ER - ...
TY - GEN. T1 - The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) suppresses proliferation and invasion of human oral squamous carcinoma cells via p53 independent and MMP, uPAR dependent mechanism. AU - Eun, Ju Lee. AU - Jin, Ha Whang. AU - Nam, Kyeong Jeon. AU - Kim, Jin. PY - 2007/1. Y1 - 2007/1. N2 - Oral squamous cell carcinomas (OSCCs) are characterized by a marked propensity for local invasion and dissemination to cervical lymph nodes. Overexpression of the epidermal growth factor receptor (EGFR) and high levels of certain matrix metalloproteinases (MMPs) have been implicated in the development of squamous cell carcinoma of oral cancer. ZD1839 (Iressa) is a quinazoline derivative that selectively inhibits the EGFR tyrosine kinase activity and is clinically used for cancer patients. This article attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level, and to characterize the effects of ZD1839 with regard to human OSCC cell ...
5,6-Dihydro-[1,2,4]triazolo[1,5-c]quinazolines. Message 1. Features of interactions between [2-(3-aryl-1H-1,2,4-triazole-5-yl)phenyl]amines, aliphatic and aromatic aldehydes
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11.7 months. Cox analysis showed that PS 0-1, recurrent disease, EGFR mutations, or EGFR-TKI treatment were associated with improved OS. In patients with EGFR-activating mutations, Cox analysis showed that patients with adenocarcinoma, recurrent disease, or EGFR-TKI treatment had significantly longer survival. Patients with EGFR-activating mutations who received EGFR-TKI therapy had a median OS of 24.3 months, which was significantly longer than
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs.We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and ...
TY - JOUR. T1 - The benefits of achieving stable disease in advanced lung cancer. AU - Kelly, Karen. PY - 2003/7. Y1 - 2003/7. N2 - The cytostatic, molecular-targeted therapies becoming available for lung cancer and other human solid tumors are more likely to result in stable disease than to produce tumor regression. In the setting of advanced lung cancer, stable disease provides significant benefit to the patient. However, in the context of clinical trials, stable disease is vaguely defined, difficult to measure, and may represent a heterogeneous patient population. The inclusion of alternative trial end points such as symptom improvement and biologic activity may help to identify patients who have achieved clinically relevant stable disease. The epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib (Iressa) has been shown to produce partial responses and stable disease in patients with advanced lung cancer who have previously received treatment with standard chemotherapies. In ...
Human being cytomegalovirus (HCMV) is a significant human being pathogen frequently connected with life-threatening disease in immunosuppressed individuals and newborns. contaminated cells. Quinazolines particularly inhibited viral early-late proteins synthesis but experienced no results at other phases from the replication routine, such as for example viral entry, in keeping with a blockage from the pUL97 function. As opposed to epithelial development element receptor inhibitors, quinazolines affected HCMV replication even though these were added hours after disease adsorption. Therefore, our results indicate that quinazolines are extremely effective inhibitors of HCMV replication in vitro by focusing on pUL97 proteins kinase activity. Human being cytomegalovirus (HCMV) is one of the family members and is connected with severe types of human being disease (23). Main acute infection aswell as lifelong prolonged infection from the sponsor ultimately causes multiple pathological effects which, ...
2014 SCI Comparison of targeted next-generation sequencing with conventional sequencing for predicting the responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in never-smokers with lung adenocarcinoma: Lung cancer. 85(2):161~167 (3.737 ...
TY - JOUR. T1 - A randomized, phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12-01). AU - Kim, Hye Ryun. AU - Jang, Joung Soon. AU - Sun, Jong Mu. AU - Ahn, Myung Ju. AU - Kim, Dong Wan. AU - Jung, Inkyung. AU - Lee, Ki Hyeong. AU - Kim, Joo Hang. AU - Lee, Dae Ho. AU - Kim, Sang We. AU - Cho, Byoung Chul. PY - 2017. Y1 - 2017. N2 - We aimed to evaluate the efficacy of dual inhibition of epidermal growth factor receptor (EGFR) with nimotuzumab (EGFR monoclonal antibody) plus gefitinib (EGFR-tyrosine kinase inhibitor) in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. An open label, randomized, phase II trial was conducted at 6 centers; 160 patients were randomized (1:1) to either gefitinib alone or nimotuzumab (200 mg, i.v. weekly) plus gefitinib (250 mg p.o. daily) until disease progression or intolerable toxicity. The primary endpoint was progression-free ...
291457567 - EP 1243582 A1 2002-09-25 - QUINOLINE AND QUINAZOLINE DERIVATIVES AND DRUGS CONTAINING THE SAME - There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: CHEM wherein R 1 and R 2 represent hydrogen, alkyl or the like; R 3 , R 4 , R 5 , and R 6 represent hydrogen, halogen, alkyl, alkoxy or the like; R 11 and R 12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R 3 , R 4 , R 5 and R 6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R 19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.[origin: EP1243582A1] There are provided compounds which can be used in the treatment of diseases
Abstract. A phase III clinical trial showed gemcitabine chemotherapy combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib significantly improved overall survival in patients with advanced pancreatic cancer. Therefore, we studied whether addition of gemcitabine to erlotinib in cancer cells having intrinsic or acquired erlotinib resistance could restore chemosensitization in these cells. We studied the synergistic effect of erlotinib and gemcitabine in EGFR-overexpressing A-431 cells with acquired erlotinib resistance and in intrinsic erlotinib-resistant triple negative breast cancer (TNBC) BT-549, MDA-MB-231 and MDA-MB-468 cell lines. Erlotinib and gemcitabine were synergistic in both parental intrinsically erlotinib-sensitive A-431 cells (combination index = 0.69 at the effective dose [ED50]) and in two A-431 cell pools that had acquired erlotinib resistance (combination indices = 0.63 and 0.49 at ED50). The synergistic effect of erlotinib and gemcitabine on ...
Title compds. represented by the formula I [wherein Q = (hetero)arylalkyl; R1 = OH, halo, alkyl, etc.; R2, R3 = independently H, (halo)alkyl, aminocarbonylalkyl, etc.; n = 0-3; and pharmaceutically acceptable salts, solvates or solvated salts thereof] were prepd. as 5-HT6 modulators. For example, reaction of 2-chloro-4-(4-methylpiperazin-1-yl)quinazoline with N-methyl-4-chlorobenzenesulfonamide gave II in 10% yield. The radioligand binding assay showed II having Ki of 200 nM. Thus, I and their pharmaceutical compns. are useful for the treatment of 5-HT6 mediated disorders, such as Alzheimers disease, schizophrenia, obesity or Parkinsons disease. [on SciFinder(R)]. ...
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A compound of formula (I) wherein A, X, Y, Z, R.sub.1 and R.sub.24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I.sub.Kur-associated disorders, and other disorders mediated by ion channel function. ##STR00001##
Gabriella M. Nepomuceno, Katie M. Chan, Valerie Huynh, Kevin S. Martin, Jared T. Moore, Terrence E. Obrien, Luiz A E Pollo, Francisco J. Sarabia, Clarissa Tadeus, Zi Yao, David E. Anderson, James B. Ames, Jared T. Shaw ...
Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein
p,,b,INTRODUCTION: ,/b,The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients outcomes in France were assessed.,/p,,p,,b,METHODS: ,/b,A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were ...
AstraZeneca has inked a global license agreement with Synairgen, a U.K. company specializing in respiratory diseases, for SNG001, a novel, inhaled interferon beta (IFN-beta) in clinical development for treating respiratory tract viral infections in patients with severe asthma. SNG001 supports the immune system by correcting a deficiency which makes patients vulnerable to respiratory tract viral infections.. AstraZeneca will pay Synairgen a $7.25 million up-front fee and potential development, regulatory and commercial milestones of up to $225 million. In addition, AstraZeneca will pay tiered royalties ranging from single-digit up to mid-teens on commercial sales. AstraZeneca will be responsible for future development costs.. In early 2015, AstraZeneca will commence a phase IIa study in patients with severe asthma, building on available clinical data from an initial phase lla trial in a broad asthma population. SNG001 also provides the opportunity to expand the clinical program in other pulmonary ...
BRATISLAVA, Slovakia (AP) - Slovakias health minister says he plans to keep AstraZeneca in the countrys vaccine arsenal, speaking a day after the country suspended use of the shots after a recipient died.. Slovakia on Tuesday halted use of the two-shot AstraZeneca vaccine after its State Institute for Drug Control concluded last week that the death of a 47-year-old woman who received the AstraZeneca was likely linked to the vaccine.. AstraZeneca is still being administered, however, to those who have already gotten the first dose and are awaiting a second shot. Its currently being given to people between the ages of 18 and 44. Health Minister Vladimir Lengvarsky said the cause of womans death was still under investigation. He said another, and the main reason, for the suspension was that Slovakia does not have enough AstraZeneca shots to continue their administration.. Slovakia, like other members of the European Union, have seen a drop in deliveries from the company.. We still count on ...
Epithelial-mesenchymal transition (EMT) is normally one particular mechanism of possessed resistance to inhibitors of the skin growth factor receptor-tyrosine kinases (EGFR-TKIs) in non-small cell lung cancer (NSCLC). micro-RNA-200c, which can regulate ZEB1 adversely, was decreased in HCC4006EUr cells significantly. Our outcomes recommend that elevated can get EMT-related obtained level of resistance to EGFR-TKIs in NSCLC. Tries should end up being produced to explore concentrating on to resensitize TKI-resistant tumors. Launch Despite the advantage of skin development aspect receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancers (NSCLC) sufferers with mutation [1], obtained level of resistance to these therapies is normally a vital scientific issue. Although the Testosterone levels790M supplementary mutation [2] and gene amplification [3] may jointly accounts for 70% of this level of resistance, systems for the staying 30% are unsure. The epithelial-mesenchymal ...
Objectives and Background To reveal the details system of miR-484 in myocardial ischemia-reperfusion (MI/R) damage. appearance of caspase-3/9 had been elevated in IR-C group. Weighed against the I/R Slc2a4 and IR-C groupings, the apoptotic index of myocardial cells in the ischemic area was reduced, the membrane potential was elevated, as well as the expression of caspase-3/9 was decreased in the miR group significantly. SMAD7 was the mark gene of miR-484. Conclusions MiR-484 protected myocardial cells from We/R damage by suppressing caspase-9 and caspase-3 appearance during cardiomyocyte apoptosis. MiR-484 decreased the appearance of IL-6, TNF-, and IL-1 in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells. Keywords: Apoptosis, Mitochondrial membrane potential, Caspase-3, Caspase-9 Launch Ischemia-reperfusion (I/R) damage is the injury caused when blood supply returns to the tissue after a period of ischemia. It is a Pyrazinamide complex process ...
Gefitinib, as the first epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC), has been proved to significantly improve the progression-free survival (PFS) in the first-line setting but suffers from resistance 7-10 months after treatment initiation. Apatinib (YN968D1), a potent vascular endothelial growth factor receptor (VEGFR) 2-TKI, specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect. Concurrent inhibition of VEGFR and EGFR pathways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC. This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting. This multicenter, randomized, double-blind, placebo-controlled phase III study (NCT02824458) has been designed to assess the efficacy and safety of apatinib or placebo
Lung cancer is the leading cause of cancer-related mortality for both men and women in United States and is estimated to remain the most fatal cancer-related malignancy (1). Little improvement in the efficacy of chemotherapy has been made in the last 20 years, usually attributed to the overexpression and overactivity of EGFR in NSCLC (4, 29-31). However, the use of selective EGFR tyrosine kinase inhibitors (gefitinib) and monoclonal antibodies against EGFR toward the treatment of lung cancer has continuously failed (32, 33). Therefore, additional alternative therapies with low toxicity and increased efficacy should be explored. Although recent studies suggest that nonpsychoactive synthetic cannabinoids possess antitumor effects against various tumors, including breast cancer, not much is known about the effects of synthetic CB1/CB2 agonists on NSCLC growth and metastasis. In the present study, we analyzed the antitumorigenic and antimetastasis effects of CB1/CB2 agonists Win55,212-2 and CB2 ...
Simotinib, also known as SIM6802, is a novel oral epidermal growth factor receptor tyrosine kinase inhibitor with potential anticancer activity. Simotinib has demonstrated equal or superior antineoplastic activities to erlotinib in preclinical studies.
The molecular mechanisms underlying erlotinib resistance in breast cancer have not been well defined. In our screening of breast cancer cell lines, down-regulation of CDK2 after treatment with erlotinib showed association with erlotinib sensitivity. Moreover, our study provides that erlotinib sensitivity is causally linked with CDK2 activity, indicating that erlotinib sensitivity depends, at least in part, on CDK2 activity. Some reports have indicated that the growth-inhibitory effect induced by EGFR-TKIs in sensitive cell lines depends mainly on G1 cell cycle arrest (1, 7, 11, 13); others have shown CDK2 activity to be down-regulated after treatment with an EGFR-TKI (12, 13). However, this is the first report establishing cause and effect relationship between erlotinib sensitivity and CDK2 activity.. The erlotinib sensitivity of breast cancer cell lines has clinical relevance for several reasons. The limited clinical activity of EGFR-TKIs in breast cancer was also echoed by the findings of this ...
Protein tyrosine kinase 2 (PTK2) expression has been reported in various types of human epithelial cancers including lung cancer; however, the role of PTK2 in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has not been elucidated. We previously reported that pemetrexed-resistant NSCLC cell line PC-9/PEM also acquired EGFR-TKI resistance with constitutive Akt activation, but we could not find a therapeutic target. Cell viability in EGFR-mutant NSCLC cell lines was measured by the WST-8 assay. Phosphorylation antibody array assay for receptor tyrosine kinases was performed in PC-9 and PC-9/PEM cell lines. We evaluated the efficacy of EGFR and PTK2 co-inhibition in EGFR-TKI-resistant NSCLC in vitro. Oral defactinib and osimertinib were administered in mice bearing subcutaneous xenografts to evaluate the efficacy of the treatment combination in vivo. Both the PTK2 phosphorylation and the treatment combination efficacy were evaluated in erlotinib-resistant EGFR-mutant NSCLC
Product Description Product Description Erlotinib hydrochloride For Treat Non-small Cell Lung Cancer 183319-69-9 Erlotinib hydrochloride---------Basic info Product Name Erlotinib hydrochloride CAS 183319-69-9 MF C22H24ClN3O4 MW 429.9 Chemical Properties Off-White Solid Usage Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic Erlotinib HCl is an HER1/EGFR inhibitor with IC50 of 2 nM. Erlotinib HCl (OSI-744) is an…
The first-generation epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib have been incorporated into treatment paradigms for patients with advanced non-small cell lung cancer. These agents are particularly effective in a subset of patients whose tumors harbor activati …
Monitor impact of Healthy Heart Africa programme and expand to other regions. AstraZeneca can evaluate the impact of its hypertension-focused Healthy Heart Africa programme in Kenya and consider expanding it to other non-communicable diseases (NCDs) and countries/regions. It can use the lessons learned from this programme to update its overall access strategy.. Broaden IP access strategy to include NCDs. AstraZeneca can expand the reach of programmes such as Healthy Heart Africa by licensing products for NCDs. For Healthy Heart Africa, this could include ticagrelor (Brilinta®), a first-line option for preventing atherothrombotic events. This could make AstraZeneca the first company to license a product targeting an NCD. A first step would be to explicitly include NCD products in its commitment to licensing.. Further expand partnerships with academia for R&D capacity building. AstraZeneca can build on its growing focus on academic partnerships in the UK to include public research organisations ...
Georgian health officials have decided to continue vaccination with AstraZeneca only for individuals over 55 years of age following statements from the European Medicines Agency and the World Health Organisation that say that unusual blood clots should be listed as a very rare side effect of the AstraZeneca vaccine for Covid-19, Trend reports citing Agenda.ge.. Today, the board of experts discussed and recommended continuing vaccination with AstraZeneca in the age group over 55, no further expansion will be made in terms of age group for AstraZeneca, Georgian deputy Health Minister Tamar Gabunia said.. She said that the delivery of the AstraZeneca vaccination will continue in Georgia as the circle of people over 55 is quite wide.. AstraZeneca has quite good results in the elderly, Gabunia added.. In the UK alone, as of March 31 there had been 79 reports of rare blood clots with low platelets, some in the brain, it was revealed on Wednesday. ...
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for ,7,800 proteins, ,300 protein kinases, and ,15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance. Our data-driven approach confirmed previously described mechanisms of resistance (e.g., AXL overexpression and PIK3 reactivation), revealed novel pharmacologically actionable targets, and confirmed the expectation of significant heterogeneity in molecular resistance drivers inducing distinct phenotypic changes. Furthermore, our approach identified an ...
Author Disclosures: T. Ueland: None. A. Åkerblom: Research Grant; Significant; AstraZeneca (institutional grant), Roche (institutional grant). T. Ghukasyan: Research Grant; Significant; AstraZeneca (institutional grant), Roche (institutional grant). A.E. Michelsen: None. P. Aukrust: None. R.C. Becker: Consultant/Advisory Board; Modest; Janssen (scientific advisory board member), AstraZeneca (scientific advisory board member), Portola (safety reviewing committee member), Merck. M. Bertilsson: Research Grant; Significant; AstraZeneca (institutional grant), Roche (institutional grant). A. Himmelmann: Employment; Significant; AstraZeneca. S.K. James: Research Grant; Significant; AstraZeneca (institutional grant), Abbot vascular (institutional grant), Roche (institutional grant). Honoraria; Modest; AstraZeneca, The Medicines Company, Bayer. Consultant/Advisory Board; Modest; AstraZeneca. A. Siegbahn: Research Grant; Significant; Bristol-Myers Squibb (institutional grant), AstraZeneca (institutional ...
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are current treatments for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR gene mutations. Although studies show an increased progression free survival (PFS) with use of EGFR TKIs in the first-line setting, most patients will develop resistance to therapy after the first about 10 months. Undoubtedly it is critical to choose an optimal clinical strategy for patients with EGFR sensitive mutation undergoing EGFR-TKI resistance. The second biopsy should be applied under condition permission to verify specific resistance mechanism. Here we discussed the mechanism of drug resistance and the choice of therapeutic regimen, also compared the superior and inferior of each treatment plan, which proposed a novel perspective for NSCLC target therapy.
Colon cancer is one of the most common human malignancies and the second leading cause of cancer death in North America just behind lung cancer. Advanced disease is associated with a poor prognosis and a 5-year survival rate of ,5% ( 35). 5-Fluorouracil with leucovorin has been the primary chemotherapy regimen for advanced colorectal cancer patients. New cytotoxic compounds are now available, including oral fluoropyrimidines, the topoisomerase I inhibitor, irinotecan (CPT-11), and the third-generation platinum compound oxaliplatin. However, these agents have not had dramatic effects on advanced disease. Novel approaches that selectively target deregulated molecular events in colon cancer cells are under development, such as targeting EGFR by monoclonal antibodies or small-molecule TKIs.. The currently available EGFR TKIs are structurally related to quinazoline, pyridopyrimidine, and pyrrolopyrimidine developed during the past decade ( 36). Quinazolines, such as AG1478, are potent EGFR ...
The EGFR pathway has been an attractive target because it is dysregulated in a significant fraction of malignant gliomas through overexpression, amplification, and activating mutations (Rich et al., 2004). Moreover, recent studies have demonstrated that EGFRvIII is required for tumor maintenance in glioma (Mukasa et al., 2010). The EGFR tyrosine kinase inhibitor gefitinib has been evaluated in a number of clinical trials for GBM; however, results have been disappointing (Rich et al., 2004; Lieberman et al., 2004). The failure of gefitinib raises questions pertaining to delivery of drug to its target. Active efflux at the BBB could prevent drugs from attaining therapeutic levels in the brain and is probably one of the main reasons behind resistance to chemotherapy. It has been shown that several other tyrosine kinase inhibitors are avid substrates for P-gp and BCRP and that their brain distribution is limited due to active efflux out of the brain (Dai et al., 2003; Chen et al., 2009; Lagas et ...
Prophylactic minocycline and reactive treatment are both acceptable options for treatment of erlotinib-induced rash in non-small cell lung cancer (NSCLC).
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Purpose:Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant lung cancer cells by activating Met and the downstream PI3K/Akt pathway. Moreover, continuous exposure to HGF accelerates the emergence of EGFR-TKI-resistant clones. We assayed whether a new Met kinase inhibitor, E7050, which is currently being evaluated in clinical trials, could overcome these three mechanisms of resistance to EGFR-TKIs. Experimental Design:The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR-mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion, and H1975 with an T790M secondary mutation. PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into SCID mice and the therapeutic effects of E7050 plus gefitinib were assayed. ...
Purpose: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR-tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity.. Experimental Design: Chemotherapy-naïve patients with advanced non-small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics.. Results: Patients (223) from five clinical trials were ...
Anthony joined AstraZeneca in 2014, holding a wealth of experience in exploratory clinical development across the pharmaceutical industry and academia. In his role he has recruited world- leading MD.PhDs and significantly improved both translational clinical science and operations, such as clinical trial cycle times. He oversees the iDecide program including REACT which focuses on real time visualisation and analysis of clinical trial data, while incorporating patient perspectives. REACT allows AstraZeneca to improve clinical trial design and ultimately enables patients to receive medicines more quickly.. Anthony is a Fellow at Homerton College, University of Cambridge and, prior to AstraZeneca, was a Board Director for Cardioxyl (2012-2015) and Rgenix (2014-2015), and a Venture Partner at OrbiMed Advisors, a global healthcare-only investment firm (2012-2013). Preceding his life sciences investment experience, he led exploratory clinical development as Vice President, Discovery Medicine Clinical ...
London, March 23: A large trial in the US and two South American countries of the Oxford-AstraZeneca vaccine has shown 79 per cent efficacy rate at preventing symptomatic COVID-19 and 100 per cent effectiveness in stopping severe disease and hospitalisation, the biotech firm said.. A Phase III study of the vaccine, developed by Oxford University and produced by AstraZeneca was conducted by AstraZeneca plc in the US, Chile and Peru and reaffirmed that the vaccine is safe and highly effective , adding to previous trial data from the UK, Brazil and South Africa.. The Oxford/AstraZeneca vaccine is also being produced as part of a tie-up by the Serum Institute of India.. The vaccines efficacy was consistent across ethnicity and age, and in participants aged 65 years and over, its effectiveness was 80 per cent.. These results are great news as they show the remarkable efficacy of the vaccine in a new population and are consistent with the results from Oxford-led trials, said Andrew Pollard, Professor ...
AP) - The European Union and drugmaker AstraZeneca say they reached a deal to end a damaging legal battle over the slow pace of deliveries of the companys COVID-19 vaccines. The European Commission said Friday that AstraZeneca made a firm commitment to deliver a total of 300 million vaccine doses by March. The commission said it involves the pharmaceutical company providing 135 million doses by the end of this year plus another 65 million doses in the first quarter of 2022. Around 100 million have already been supplied. Brussels says the deliveries would respect an advance purchasing agreement the EU reached with AstraZeneca a year ago. ...
Pfizer has announced a deal with AstraZeneca for exclusive over-the-counter (OTC) rights to market Nexium for approved indications in the United States, Europe and the rest of the world.. Under the terms of the agreement, Pfizer will make an upfront payment of $250 million to AstraZeneca, who will be eligible to receive milestone and loyalty payments based on product launches and sales.. Proton pump inhibitor, Nexium (esomeprazole magnesium), is a leading prescription drug currently approved to treat patients with the symptoms of gastroesophageal reflux disease (GERD). It was launched by AZ in Europe in 2000, and a year later in the US.. Nexium is one of the most recognised and respected products in its class with tremendous brand equity and loyalty. We are proud to be AstraZenecas partner of choice for OTC Nexium, said Paul Sturman, Pfizer Consumer Healthcare President.. By working with AstraZeneca to offer upon regulatory approval an over-the-counter version of Nexium - a brand people know ...
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TY - JOUR. T1 - The role of MET activation in determining the sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors. AU - Rho, Jin Kyung. AU - Choi, Yun Jung. AU - Lee, Jin Kyung. AU - Ryoo, Baek Yeol. AU - Na, Im Il. AU - Yang, Sung Hyun. AU - Lee, Seung Sook. AU - Kim, Cheol Hyeon. AU - Yoo, Young Do. AU - Lee, Jae Cheol. PY - 2009/10. Y1 - 2009/10. N2 - The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) seems almost inevitable, even in patients with lung cancer that initially respond well to EGFR-TKIs. MET amplification was recently found to be a mechanism of escape from the anticancer effect of EGFR inhibitors. In the present study, we investigated the means whereby MET affects sensitivity to EGFR-TKIs in PC-9 cells. Gefitinib- or erlotinib-resistant sublines were established by exposing the parental PC-9 cell line to chronic, repeated treatments with these drugs. These resistant sublines showed more than 100-fold more ...
Title: Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and New Therapeutic Perspectives in Non Small Cell Lung Cancer. VOLUME: 12 ISSUE: 6. Author(s):Laura Bonanno, Antonio Jirillo and Adolfo Favaretto. Affiliation:Medical Oncology 2, Istituto Oncologico Veneto-IRCCS, Via Gattamelata, 64, 35128 Padova, Italy.. Keywords:EGFR, Tyrosine kinase inhibitors, resistance, mutations, amplifications, MET, VEGFR, NSCLC, Gefitinib, Erlotinib. Abstract: EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of ...
This trial will investigate the efficacy and tolerability of epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, in combination with
Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. However, 25% to 30% of patients with EGFR-activating mutations show intrinsic resistance, and the responders invariably acquire resistance to gefitinib. Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR-activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. Strong immunoreactivity for HGF in cancer cells was detected in lung adenocarcinoma patients harboring EGFR-activating mutations, but no T790M mutation or MET amplification, who showed intrinsic or acquired resistance to gefitinib. The findings indicate that HGF-mediated MET activation is a novel mechanism of gefitinib resistance in lung adenocarcinoma with EGFR-activating mutations. Therefore, ...
TY - JOUR. T1 - Disruption of ETV6 leads to TWIST1-dependent progression and resistance to epidermal growth factor receptor tyrosine kinase inhibitors in prostate cancer. AU - Tsai, Yuan Chin. AU - Zeng, Tao. AU - Abou-Kheir, Wassim. AU - Yeh, Hsiu Lien. AU - Yin, Juan Juan. AU - Lee, Yi Chao. AU - Chen, Wei Yu. AU - Liu, Yen Nien. N1 - Funding Information: This work was supported by the Ministry of Science and Technology of Taiwan to YCT (MOST104-2320-B-038-055-MY3), WYC (MOST106-2320-B-038-057), and YNL (MOST104-2314-B-038-045-MY3 and MOST105-2628-B-038 -006 -MY3), by Taipei Medical University-Wan Fang Hospital to WYC (105TMU-WFH-04), by the National Health Research Institutes of Taiwan to YNL (NHRI-EX107-10702BI), and by the Health and Welfare Surcharge of Tobacco Products to YNL (MOHW106-TDU-B-212-144001).. PY - 2018/2/19. Y1 - 2018/2/19. N2 - Background: ETS variant gene 6 (ETV6) is a putative tumor suppressor and repressed by epidermal growth factor receptor (EGFR) signaling in prostate ...
Serotonin receptors play a variety of functional roles in the body. Some indications and treatment claims for one of the classes of serotonin receptors, the 5-HT3 receptor family, include: anxiety, depression, chemotherapy- and radiation-induced emesis, constipation, irritable bowel syndrome, pain, drug addiction, and satiety control. A 5-HT3 receptor partial agonist, MD-354, served as a lead compound in the development of new 5-HT3 receptor ligands. Using halogenated analogs the study investigated their effect on binding to the 5-HT3 receptor. Conformationally-constrained analogs (quinazolines) were shown to be a novel class of 5-HT3 receptor antagonists. The log P values were determined for several analogs, and indicated that these ligands should be able to penetrate the blood-brain barrier. A homology model of the 5-HT3 receptor was built and the docking modes were assessed for these two series. Quinazolines were investigated for antidepressant properties using the mouse tail suspension test, and
TY - JOUR. T1 - Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene. T2 - A case report. AU - Mody, Kabir. AU - Strauss, Edward. AU - Lincer, Robert. AU - Frank, Richard C.. PY - 2010/10/20. Y1 - 2010/10/20. N2 - Background: Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene.Case presentation: A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine ...
Gefitinib and erlotinib were the first EGFR tyrosine kinase inhibitors (TKIs) that were approved for the treatment of patients with non-small cell lung cancer (NSCLC). These drugs inhibit kinase activity through competitively interacting with the ATP-binding site of EGFR, preventing autophosphorylation and consequently inhibiting downstream signaling. This inhibition leads to apoptosis in cells dependent on EGFR signaling, such as those with EGFR mutations.. Gefitinib efficacy was first evaluated in 2 single-arm phase II studies in patients with NSCLC who had received prior chemotherapy. The success of these trials led to the accelerated approval of gefitinib in 20034,5 and initiation of a phase III trial6 (ISEL), which randomized patients to gefitinib versus placebo and found no difference in median survival (5.6 vs. 5.1 months, respectively). The lack of an overall survival benefit in ISEL prompted the FDA to restrict gefitinib use. Notably, these early studies did not select or evaluate ...
TY - JOUR. T1 - Epidermal growth factor receptor (EGFR)-tyrosine Kinase inhibitor treatment and salvage chemotherapy in EGFR-mutated elderly pulmonary adenocarcinoma patients. AU - Tseng, Yen Han. AU - Tseng, Yen Chiang. AU - Lin, Yi Hsuan. AU - Lee, Yu Chin. AU - Perng, Reury Perng. AU - Whang-Peng, Jacqueline. AU - Chen, Yuh Min. PY - 2015/6/8. Y1 - 2015/6/8. N2 - Background. Lung cancer is frequently a disease of elderly patients. However, these patients are often treated less actively owing to a higher comorbidity rate and poor performance status. The efficacy of different treatments in elderly patients with epidermal growth factor receptor (EGFR)-mutated lung cancer is still unknown. Materials and Methods. We retrospectively reviewed the records of our pulmonary adenocarcinoma patients treated between 2010 and 2013. Data on patient age, type of tumor EGFR mutation, response to first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, type of salvage chemotherapy, and efficacy of EGFR-TKI ...
A number of different strategies have been explored to therapeutically modulate tumor oxygenation. The studies described here show that the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib improves oxygenation within A431 squamous cell carcinoma xenografts. Using in vivo PET imaging with the hypoxia marker FAZA, it was seen that treatment with gefitinib reduced hypoxia in A431 xenografts in comparison with untreated control tumors. Importantly, serial PET imaging studies were able to show that gefitinib reduced hypoxia compared with pretreatment levels. These findings were verified in a parallel experiment in which hypoxia was assessed using pimonidazole binding at time points corresponding with the PET studies.. In vivo imaging of hypoxia was conducted using the PET hypoxia imaging agent FAZA. This compound displays different physical properties to fluoromisonidazole, in particular, a lower octanol/water partition coefficient, indicating the potential for more rapid ...
Conventional chemotherapeutic regimens have reached an efficacy plateau against most solid tumors and deal with significant toxicity. Recently, the goal of the oncologic research to improve outcome and reduce treatment-related side-effects has led to the development of novel anticancer treatments targeting specific proteins or genes involved in cancer growth and progression. In particular, the tyrosine-kinase inhibitors (TKIs) gefitinib and erlotinib targeting the epidermal growth factor receptor (EGFR) have been approved for the treatment of non-small-cell lung cancer (NSCLC). Their clinical activity has been related to different clinical and biological parameters, such as the presence of activating mutations in the kinase domain of the target. Disappointingly, their clinical efficacy is limited by the development of resistance which is caused in more than 50% of the cases by the emergence of a secondary point-mutation (T790M) in the ATP-binding cleft of EGFR. Several novel EGFR inhibitors, ...
Lung cancer is the most common cause of cancer deaths in Korea [7]. Traditional therapy, including resection, platinum-based chemotherapy and radiation therapy, have only limited therapeutic value. Therefore, the 5-year survival rate of lung cancer has not changed significantly in the past 30 years [8].. EGFR TKI therapy, which specifically targets EGFR, was recently introduced and provided guidance in this situation. Targeting EGFR in patients with activating EGFR mutations has shown initial and significant success in practice [1]. Unfortunately, the vast majority of patients develop resistance to the treatment, typically in less than 1 year. In this situation, understanding the mechanism of the resistance became very important.. Most of the mechanisms that lead to EGFR TKI resistance involve an additional mutation, such as a T790M mutation, or amplification of alternative pathways. In addition, morphological transformation is also a well-known mechanism. The most well known example of this ...
TY - JOUR. T1 - Mechanisms and overcome of acquired resistance to EGFR tyrosine kinase inhibitors. AU - Soh, Junichi. AU - Toyooka, Shinichi. AU - Ueno, Tsuyoshi. AU - Miyoshi, Shinichiro. PY - 2012/4. Y1 - 2012/4. N2 - Development of effective therapies for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, which account for approximately 40% of lung adenocarcinoma patients in Japan, is important to improve the clinical outcome of NSCLC. EGFR-mutant NSCLCs are sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and elucidating the binding affinity of adenosine triphosphate (ATP) and EGFR-TKI to wild type or mutant EGFR helps our understanding of the mechanisms of resistance to EGFR-TKI. The mechanisms of acquired resistance to EGFR-TKIs are broadly classified into two categories: 1) secondly acquired EGFR mutations including T790M and 2) oncogene kinase switch such as MET gene amplification. To overcome the acquired resistance, it is ...
Pharma company AstraZeneca has publicly released preclinical data from more than 50 of its medicines in order to find new drug combinations for cancer treatments. The data AstraZeneca released will be used in a competition it created in partnership with the DREAM Challenge, a non-profit, collaborative community that runs crowdsourcing efforts for biology.. People who participate in the challenge will develop computer models that identify the properties of drugs that make them powerful when combined. Anyone who has the training or expertise to work with these models is invited to participate. The winners of AstraZenecas challenge will be able to submit their prediction for publication in the journal Nature Biotechnology.. Other organizations that partnered with AstraZeneca for the challenge, which is called AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge, include the Wellcome Trust Sanger Institute, the European Bioinformatic Institute, and Sage Bionetworks.. AstraZeneca has a ...
The EGFR TKI erlotinib was shown to result in increased survival in previous clinical trials when used as monotherapy in previously treated patients with advanced NSCLC [30]. Toxicity to erlotinib is markedly lower than many alternative pharmacologic treatments, and would clearly be a preferred therapeutic option if survival was shown to be equivalent or better than treatment with other second line agents. Since only a fraction of patients respond to such therapy, a priori identification of responders could have a vast effect on survival. Many clinical parameters which have been shown to correlate with response to EGFR TKIs, including smoking history, gender, ethnicity, and tumor histology. Additionally, EGFR expression levels, phosphorylation status of EGFR, and mutations within the kinase domain [22, 28, 31] also correlate with sensitivity to some degree. While each of these predictors of response result in some overlap, potential responders to EGFR targeted therapeutics may be overlooked. In ...
TY - JOUR. T1 - Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung. T2 - Okayama Lung Cancer Study Group experience. AU - Hotta, Katsuyuki. AU - Kiura, Katsuyuki. AU - Takigawa, Nagio. AU - Kuyama, Shoichi. AU - Segawa, Yoshihiko. AU - Yonei, Toshiro. AU - Gemba, Kenichi. AU - Aoe, Keisuke. AU - Shibayama, Takuo. AU - Matsuo, Keisuke. AU - Kamei, Haruhito. AU - Fujiwara, Yoshiro. AU - Bessho, Akihiko. AU - Moritaka, Tomonori. AU - Sugimoto, Keisuke. AU - Tabata, Masahiro. AU - Ueoka, Hiroshi. AU - Tanimoto, Mitsune. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/1. Y1 - 2009/1. N2 - Background: Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma. Methods: We ...
Saccharin belongs to a class of cyclic sulfonamides and this is used as an artificial sweetener for a longtime. The benzothiazole and quinazoline derivatives form an important classes of fused heterocyclic compounds with a wide range of biological activities such as antimicrobial (Schwartz et al., 1992), anticancer (Wolfe et al., 1990), antiinflammatory (Tereshima et al., 1995). As a part of our studies in this area, the molecular and crystal structures of the title compound have been determined and the results are presented here.. The title compound comprises a benzothiazole ring fused with quinazoline ring. X-ray analysis confirms the molecular structure and atom connectivity as illustrated in Fig. 1. The benzothiazole ring system is essentially planar with a maximum deviation of -0.0127 (16)Å for the C7 atom. The quinazoline ring system is also essentially planar with the maximum deviation of -0.1588 (15)Å for the N1 atom. The dihedral angle between the benzothiazole and quinazoline ring ...
Results In C57BL/6 mice, gefitinib decreased Cxcl1 and Cxcl2 expression by gastric epithelial cells, myeloperoxidase-positive inflammatory cells in the mucosa and epithelial DNA damage induced by H. pylori infection. Similar reductions in chemokines, inflammatory cells and DNA damage occurred in infected EgfrΔepi versus Egfrfl/fl control mice. In H. pylori-infected transgenic insulin-gastrin (INS-GAS) mice and gerbils, gefitinib treatment markedly reduced dysplasia and carcinoma. Gefitinib blocked H. pylori-induced activation of mitogen-activated protein kinase 1/3 (MAPK1/3) and activator protein 1 in gastric epithelial cells, resulting in inhibition of chemokine synthesis. MAPK1/3 phosphorylation and JUN activation was reduced in gastric tissues from infected wild-type and INS-GAS mice treated with gefitinib and in primary epithelial cells from EfgrΔepi versus Egfrfl/fl mice. Epithelial EGFR activation persisted in humans and mice after H. pylori eradication, and gefitinib reduced gastric ...
AMPRENAVIR EXPANDED ACCESS PROGRAM ANNOUNCED TODAY. Glaxo Wellcome announced today (9/21) that the amprenavir expanded access program is starting for both adults and children (,4 yrs). You or your doctor can call-. 1-800-248-9757 immediately to receive information about enrollment. You or your doctor can call to give the company your doctors name and address. On Sept 28 they will send out expanded access program binders explaining the program. As soon as a person is enrolled in the program drug will be sent out. The company is submitting their NDA to the FDA for accelerated approval in October. Review and approval can take usually from 3-6 months, meaning approval will not come sooner than January 1999.. The program is uniquely offering 3 options for accessing amprenair-. 1. Individuals experiencing adverse side effects from their current PI regimen such as lipodystrophy or elevated lipids but are not failing their current PI regimen can enroll in this option. The purpose is to try and collect ...
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect. PATIENTS AND METHODS: A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS). RESULTS: Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% ...
As part of a plan to focus its research activities on fewer therapeutic areas, AstraZeneca is shutting down its Avishkar R&D site in Bangalore, India. The closure will cost 168 jobs in pharmaceutical development and drug discovery for neglected tropical diseases, tuberculosis, and malaria, all areas AstraZeneca will not pursue further. Work will continue on AZD5847, in Phase II studies for tuberculosis, and AstraZeneca will still make available its compound library to open-innovation partners.. ...
Emergency Use Listing granted to AstraZeneca and Serum Institute of India enabling global access to the vaccine. AstraZenecas COVID-19 vaccine has been granted Emergency Use Listing (EUL) by the World Health Organization (WHO) for active immunisation to prevent COVID-19 in individuals 18 years of age and older, including those over 65.. The authorisation of COVID-19 Vaccine AstraZeneca manufactured by AstraZeneca, and COVISHIELD manufactured by Serum Institute of India (SII), enables global access to the vaccine during the pandemic.. The EUL allows for two doses of the vaccine to be administered at a four to 12-week interval. This regimen was shown in clinical trials to be safe and effective in preventing symptomatic COVID-19, with no severe cases and no hospitalisations more than 14 days after the second dose. The WHOs Strategic Advisory Group of Experts on Immunization (SAGE) recommended a dosing interval of eight to 12 weeks. In addition, they also recommended use of the vaccine in ...
Disclosure of Interest D. Pappas Employee of: CORRONA, Inc., Paid instructor for: Novartis, K. Lampl Shareholder of: AstraZeneca, Employee of: AstraZeneca, J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc., S. Radominski Grant/research support: Pfizer,BMS,AstraZeneca, Amgen, Sanofi, Novartis, Celltrion, Roche;, Consultant for: Pfizer,BMS,AstraZeneca, Employee of: Universidade Federal do Parana- Curitiba- Brzazil;, Speakers bureau: Pfizer,BMS,AstraZeneca,Janssen,Sanofi, GSK, J. Gal: None declared, F. Nyberg Shareholder of: AstraZeneca, Employee of: AstraZeneca, A. Malaviya Consultant for: Part-time Consultant Rheumatologist at ISIC Hospital, Advisory Board Member Janssen Pharma, Roche Pharma, Pfizer Pharma, Sanofi Pharma, A. Whitworth Employee of: CORRONA, Inc., O. Rillo: None declared, A. Gibofsky Shareholder of: Amgen, BMS, GlaxoSmithKline, Johnson & Johnson, Pfizer, Roche, Consultant for: Amgen, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche, Antares, UCB, Speakers ...
Astrazeneca News Headlines. AZN Share News. Financial News Articles for Astrazeneca Plc Ord Shs $0.25 updated throughout the day.
At present, the third generation of platinum-based regimens (NCCN clinical practice guidelines recommended the use of vinorelbine or gemcitabine, or Taxol, etc.) is the first-line treatment for advanced lung cancer patients. Its effective rate is 20-30%, the median survival time is 7-9 months, 1-year and 2-year survival rate is 31-36% and 10-13% respectively. The efficacy has reached the platform and it is difficult to have more breakthroughs. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as Iressa and Erlotinib have proved effective in first or second line therapy for advanced non-small cell lung cancer(NSCLC).First-SIGNAL and IPASS research have laid first-line status for gefitinib in treatment of NSCLC and the progression-free survival time was maintained at 9-10 months. EGFR-TKIs treatment is simple, well tolerated, drug side effects, etc. There are also a rash, diarrhea and other adverse reactions, affecting the quality of life of patients with serious or even ...
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) will be the 1st\line treatment for individuals with mutant non\little\cell lung cancer (NSCLC). in the osimertinib group (= 41) vs the platinum\pemetrexed group (= 22; risk percentage 0.27; 95% self-confidence period, 0.13\0.56). The median PFS was 12.5 and 4.three months in the osimertinib and platinum\pemetrexed groups, respectively. Quality 3 adverse MK-5172 hydrate IC50 occasions determined to become linked to treatment happened in 5 individuals (12.2%) treated with osimertinib and 12 individuals (54.5%) treated with platinum\pemetrexed. The security and effectiveness leads to this subanalysis are in keeping with the outcomes of the entire AURA3 research, and support the usage of osimertinib in Japanese individuals with T790M mutation\positive NSCLC whose disease offers progressed following 1st\collection EGFR\TKI treatment. (ClinicalTrials.gov trial sign up zero. NCT02151981.) gene resulting in T790M is situated in ...
Zeinyeh W, Esvan YJ, Josselin B, Baratte B, Bach S, Nauton L, Théry V, Ruchaud S, Anizon F, Giraud F, Moreau P. Kinase inhibitions in pyrido[4,3-h] and [3,4-g]quinazolines: Synthesis, SAR and molecular modeling studies. Bioorg Med Chem. 2019 May 15;27(10):2083-2089. doi: 10.1016/j.bmc.2019.04.005.. Chassé H., Boulben S., Glippa V., Pontheaux F., Cormier P., Morales J. (2019) In vivo analysis of protein translation activity in sea urchin eggs and embryos. Methods in Cell Biol Vol. 151, doi: 10.1016/bs.mcb.2018.10.008. Falaise C, Cormier P, Tremblay R, Audet C, Deschênes JS, Turcotte F, François C, Seger A, Hallegraeff G, Lindquist N, Sirjacobs D, Gobert S, Lejeune P, Demoulin V, Mouget JL. (2019) Harmful or harmless: Biological effects of marennine on marine organisms. Aquat Toxicol. 209:13-25. doi: 10.1016/j.aquatox.2019.01.016.. Chassé H., Boulben S., Cormier P., Morales J. (2019) Translational control of canonical and non-canonical translation initiation factors at the sea urchin egg to ...
ROS1 is a receptor tyrosine kinase (encoded by the gene ROS1) with structural similarity to the anaplastic lymphoma kinase (ALK) protein; it is encoded by the c-ros oncogene and was first identified in 1986.[7][8][9][10] The exact role of the ROS1 protein in normal development, as well as its normal physiologic ligand, have not been defined.[8] Nonetheless, as gene rearrangement events involving ROS1 have been described in lung and other cancers, and since such tumors have been found to be remarkably responsive to small molecule tyrosine kinase inhibitors, interest in identifying ROS1 rearrangements as a therapeutic target in cancer has been increasing.[7][11] Recently, the small molecule tyrosine kinase inhibitor, crizotinib, was approved for the treatment of patients with metastatic NSCLC whose tumors are ROS1 -positive.[12]. Gene rearrangements involving the ROS1 gene were first detected in glioblastoma tumors and cell lines.[13][14] In 2007 a ROS1 rearrangement was identified in a cell line ...
RNS Number: 0958 T AstraZeneca PLC 18 March 2019 18 March 2019 07:00 GMT. US FDA grants saracatinib Orphan Drug Designation. The US Food and Drug...
OncoLink, the Webs first cancer resource,provides comprehensive information on coping with cancer, cancer treatments, cancer research advances, continuing medical education, cancer prevention, and clinical trials
Referenzen: 1. Schill C et al. Nicht-kleinzelliges Bronchialkarzinom. Schweiz Med Forum. 2015;15(19):453- 458. 2. Sharma SV et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169-81.. 3. Wells A et al. EGF receptor. Int J Biochem Cell Biol. 1999;31:637 -643.. 4. Wakeling A et al. ZD1839 (Iressa): An Orally Active Inhibitor of Epidermal Growth Factor Signaling with Potential for Cancer Therapy. Cancer Res. 2002;62(20):5749-54.. 5. Tapia C et al. EGFR-Mutationsanalyse beim nichtkleinzelligen Lungenkarzinom: Erfahrungen aus der Routinediagnostik. Pathologe 2009;30(5):384-392. 6. Sekine I et al. Emerging ethnic differences in lung cancer therapy. Br J Cancer. 2008;99:1757-1762.. 7. Lynch TJ et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129 -2139.. 8. Fachinformation Schweiz IRESSA® (www.swissmedicinfo.ch), M-Files Approval: 13213 (last ...
Amgen and AstraZeneca announce positive results from Phase III study of brodalumab (AMG 827) in patients with moderate-to-severe plaque psoriasis
George J. Cerniglia, Nabendu Pore, Jeff H. Tsai, Susan Schultz, Rosemarie Mick, Regine Choe, Xiaoman Xing, Turgut Durduran, Arjun G. Yodh, Sydney M. Evans, Cameron J. Koch, Stephen M. Hahn, Harry Quon, Chandra M. Sehgal, William M.F. Lee, Amit Maity ...
Currently, there is no standard salvage regimen after the failure of cisplatin-based chemotherapy for advanced urothelial carcinoma. Many novel agents have been developed and have shown modest activity in urothelial carcinoma. With the advancement of molecular biology and a deeper understanding of the pathogenesis of urothelial carcinoma, new approaches for treating patients using molecularly targeted therapies have emerged. Previous studies have shown that the over-expression of epidermal growth factor receptor (EGFR) predicts poor survival and stage progression [4, 5]. EGFR is more strongly expressed in invasive tumors (pT2-T4) and high-grade tumors than in superficial or low-grade tumors [4]. However, mutations within the kinase domain and truncations of the EGFR are rarely seen in bladder cancer, and they have emerged as attractive therapeutic targets. Cetuximab (an EGFR inhibitor) is a chimeric human/mouse monoclonal antibody that prevents dimerization by binding to the extracellular domain ...
Array Receives $1,000,000 Milestone Payment from AstraZeneca -. BOULDER, Colo., Jan. 24 /PRNewswire-FirstCall/ -- Array BioPharma Inc. (Nasdaq: ARRY) and AstraZeneca PLC selected an additional clinical candidate for their small molecule anti-cancer program, triggering a $1 million milestone payment from AstraZeneca to Array. In December 2003, Array partnered the oncology portion of its MEK program, including its lead compound, ARRY-142886 (AZD6244), for co-development and commercialization with AstraZeneca. At that time, Array and AstraZeneca established a collaboration for research and development of additional clinical candidates.. We are pleased that our collaboration with AstraZeneca has yielded an additional high quality development candidate, said Kevin Koch, Ph.D., President and Chief Scientific Officer, Array BioPharma. Our first proprietary compound, ARRY-142886, continues to make good progress in Phase Ib. We believe the data generated in this study will support more advanced ...
The AstraZeneca vaccine prompts cells to make a specific part of SARS-CoV-2 (the virus that causes COVID-19), called the spike protein, which the virus uses to attach to cells when infecting us.. The vaccine stimulates our immune system to generate antibodies against the spike protein, which then primes the body to mount an immune response against SARS-CoV-2, if it encounters the virus in the future.. But in some people, the AstraZeneca vaccine seems to produce antibodies that react with platelets, making them stick together, leading the blood to clot. This in turn reduces circulating platelet numbers, and hence the thrombocytopenia.. These antibodies are similar to those found in some people on a blood thinning drug called heparin. The immune response to heparin generates antibodies that bind to platelets. This can lead to blood clots in some people, called heparin induced thrombocytopenia. As many as one in 20 patients receiving heparin develop thrombocytopenia.. Keeping in mind were yet to ...
Using CO LOSARTAN TAB 100MG during pregnancy may raise the risk of children developing some disorder (commpon for some such kind of drugs), however it depends upon how CO LOSARTAN TAB 100MG ingredients pass through placenta and may have effect on baby - Strength of CO LOSARTAN TAB 100MG is major factor in determination of such side effects, The possible danger in pregnancy are under research. ASTRAZENECA FARMACEUTICA SPAIN, S.A Canada publish leaflet about CO LOSARTAN TAB 100MG every update to describe possible risks of using CO LOSARTAN TAB 100MG side effect in pregnancy and pregnant women. You may download ASTRAZENECA FARMACEUTICA SPAIN, S.A issued leaflet regarding side effects of CO LOSARTAN TAB 100MG - LOSARTAN POTASSIUM. Pregnancy Side Effects can be easily know by Atc code of CO LOSARTAN TAB 100MG ATC CODE.. ...
The Oxford / AstraZeneca vaccine does not use the revolutionary genetic technology of mRNA or messenger RNA like Pfizer and Moderna, but the more traditional virus-vector type that takes as a carrier another virus (a chimpanzee adenovirus) although genetically modified and adapted to combat Covid-19.. However, it has been criticized due to the confusion in the interim results of clinical trials. The British laboratory announced in November that its vaccine had an average efficacy of 70%, compared to more than 90% for the Pfizer / BioNTech and Moderna vaccines.. The efficacy of the AstraZeneca / Oxford vaccine was 90% for volunteers who received a half dose first and then a full dose one month later, but only 62% for another group that was more frequently vaccinated with two full doses with a month difference.. The half-dose injection was, in fact, due to an error and only a small group had followed the second protocol, which had raised concern, and led the company to announce on November 26 ...
The young health programme scholarship 2020 through the young health programme yhp astrazeneca works to engage and empower young people with information so that they can make healthy choices today that will lead to better health later in life. Our young health programme is a non communicable disease ncd prevention programme developed in partnership with johns hopkins bloomberg school of public health and plan international. Astrazeneca s young health global grants programme funds youth focused non profits to help them develop and deliver effective health promotion programmes especially in under resourced and marginalised communities in low and middle income countries. ...
The Food and Drug Administration (FDA) has asked hospitals and pharmacies to recall batches of rosuvastatin - a drug to control cholesterol marketed as Crestor - which the agency said had been mixed with counterfeit drugs. FDA official Chih Lan-hui (遲蘭慧) said that global biopharmaceutical company AstraZeneca received a report from a pharmacist in New Taipei City last month that its Crestor 10mg film-coated tablets might contain counterfeit drugs in similar packaging. The company confirmed the product was fake after sending a sample abroad to be examined. The FDA received the report from AstraZeneca on Thursday and the New Taipei District Prosecutors Office
FDA Approves AstraZeneca PLC (AZN)s Seroquel(R) for Maintenance Treatment in Bipolar Disorder WILMINGTON, Del., May 14 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN - News) today announced that
Both pieces of news will be welcomed by Chief Executive Pascal Soriot, who is determined to prove AstraZeneca has a strong independent future after fending off Pfizer. Many analysts believe Pfizer could repeat its bid to buy AstraZeneca later this year.. EASTERN EUROPEAN PATIENTS. The results of the so-called PLATO study into Brilinta were first reported at a medical meeting in 2009 and went on to form the basis of successful new drug applications in the United States, Europe and other markets. Brilinta was launched in 2011. [eap_ad_2] But various aspects of the study, which relied heavily on patients recruited in eastern Europe, have been criticized over the years by a number of medical experts. Poland and Hungary together accounted for 21 percent of all subjects studied - more than double the United States and Canada combined.. Two doctors, James DiNicolantonio of Ithaca, New York and Ales Tomek of Charles University in Prague, raised several questions about the conduct of the study in a paper ...
Last year, the FDA called for stronger heart-failure warnings on the label of AstraZeneca Type 2 diabetes med Onglyza. And now, AstraZeneca and former partner Bristol-Myers Squibb are being hit with 14 lawsuits related to the meds heart-failure risks.
The more than two million Canadians who received the AstraZeneca-Oxford COVID-19 vaccine made the right choice and should not regret their decision, health experts say, despite the fact that some provinces are pausing rollout of the vaccine over concerns about the risk of rare blood clots. In fact, Dr. David Naylor, co-chair of the national COVID-19 Immunity Task Force, thanked those who received the AstraZeneca vaccine, saying their actions protected them and others around them. He noted that when AstraZeneca first came into use, several provinces were in the grips of an intensifying third wave of COVID-19. The risks were obvious, with scores of Canadians dying every week and many more hospitalized, including those with illness severe enough to require intensive care and mechanical ventilation, he said in an email. It made very good sense in those circumstances to follow public health advice about taking the first vaccine on offer. Dr. Zain Chagla, an infectious diseases physician at St. Josephs
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Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
... (marketed by King Pharmaceuticals under the brand name Skelaxin) is a muscle relaxant used to relax muscles and relieve pain caused by strains, sprains, and other musculoskeletal conditions. Its exact mechanism of action is not known, but it may be due to general central nervous system depression. It is considered to be a moderately strong muscle relaxant, with relatively low incidence of side effects. Skelaxin is available in an 800 mg scored tablet. Possible side effects include nausea, vomiting, drowsiness and CNS side effects, such as dizziness, headache, and irritability. The metabolism of metaxalone involves the liver cytochrome P450 system. Based on the information in the labeling, patients receiving metaxalone therapy and physicians prescribing metaxalone are directed to take precaution when coadministering it with other medications involving the P450 system.[1][2] Because of potential for side effects, this drug is considered high risk in the elderly. As of 2015[update] the ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
While botulinum toxin is generally considered safe in a clinical setting, there can be serious side effects from its use. The use of botulinum toxin A in cerebral palsy children is safe in the upper and lower limb muscles.[5][6] Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles. Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and trouble swallowing. Side effects are not limited to direct paralysis however, and can also include headaches, flu-like symptoms, and allergic reactions.[41] Just as cosmetic treatments only last a number of months, paralysis side-effects can have the same durations.[citation needed] At least in some cases, these effects are reported to dissipate in the weeks after treatment.[citation needed] Bruising at the site of injection is not a side effect of the ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
... is a centrally acting muscle relaxant. It can be used as an antidote for strychnine poisoning. Mephenesin however presents with the major drawbacks of having a short duration of action and a much greater effect on the spinal cord than the brain, resulting in pronounced respiratory depression at clinical doses and therefore a very low therapeutic index. It is especially dangerous and potentially fatal in combination with alcohol and other depressants.[1] Mephenesin was used by Bernard Ludwig and Frank Berger to synthesize meprobamate, the first tranquilizer to see widespread clinical use. Mephenesin is no longer available in North America but is used in France, Italy and a few other countries.[2] Its use has largely been replaced by the related drug methocarbamol, which is better absorbed.[3] Mephenesin may be an NMDA receptor antagonist.[4] ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
Neuromuscular blocking agents need to fit in a space close to 2 nanometres, which resembles the molecular length of decamethonium.[13] Some molecules of decamethonium congeners may bind only to one receptive site. Flexible molecules have a greater chance of fitting receptive sites. However, the most populated conformation may not be the best-fitted one. Very flexible molecules are, in fact, weak neuromuscular inhibitors with flat dose-response curves. On the other hand, stiff or rigid molecules tend to fit well or not at all. If the lowest-energy conformation fits, the compound has high potency because there is a great concentration of molecules close to the lowest-energy conformation. Molecules can be thin but yet rigid.[14] Decamethonium for example needs relatively high energy to change the N-N distance.[13] In general, molecular rigidity contributes to potency, while size affects whether a muscle relaxant shows a polarizing or a depolarizing effect.[3] Cations must be able to flow through ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side effects of sedation, drowsiness and may cause dependence with long-term use. Several of these agents also have abuse potential, and their prescription is strictly controlled.[22][23][24] The benzodiazepines, such as diazepam, interact with the GABAA receptor in the central nervous system. While it can be used in patients with muscle spasm of almost any origin, it produces sedation in most individuals at the doses required to reduce muscle tone.[5] Baclofen is considered to be at least as effective as diazepam in reducing spasticity, and causes much less sedation. It acts as a GABA agonist at GABAB receptors in the brain and spinal cord, resulting in hyperpolarization of neurons expressing this receptor, most likely due to increased potassium ion conductance. Baclofen also inhibits neural function presynaptically, by reducing calcium ion influx, and thereby reducing the release of excitatory ...
... ( anticholinergic agent) is a group of substances that blocks the action of the neurotransmitter acetylcholine (ACh) at synapses in the central and the peripheral nervous system, and, in broad terms, neuromuscular junction.[1][2] These agents inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body;[3] cholinergic process otherwise by enhancing ACh function.[3] In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central, peripheral nervous system and neuromuscular junction:[3] antimuscarinic agents, and antinicotinic agents (ganglionic blockers, neuromuscular blockers).[4] In strict terms, anticholinergic only comprises ...
The usual dose of 350 mg is unlikely to engender prominent side effects other than somnolence, and mild to significant euphoria or dysphoria, but the euphoria is generally short-lived due to the fast metabolism of carisoprodol into meprobamate and other metabolites; the euphoria derived is, according to new research, most likely due to carisoprodol's inherent, potent anxiolytic effects that are far stronger than those produced by its primary metabolite, meprobamate, which is often misblamed for the drug-seeking associated with carisoprodol, as carisoprodol itself is responsible for the significantly more intense CNS effects than meprobamate alone. Carisoprodol has a unique mechanism of action, qualitatively different from that of meprobamate (Miltown). The medication is well-tolerated and without adverse effects in the majority of patients for whom it is indicated. In some patients, however, and/or early in therapy, carisoprodol can have the full spectrum of sedative side effects and can impair ...
InChI=1S/C40H48N2O6.2ClH/c1-41(2)17-15-27-22-34(44-6)36-24-30(27)31(41)19-25-9-12-29(13-10-25)47-40-38-28(23-37(45-7)39(40)46-8)16-18-42(3,4)32(38)20-26-11-14-33(43-5)35(21-26)48-36;;/h9-14,21-24,31-32H,15-20H2,1-8H3;2*1H/q+2;;/p-2/t31-,32+;;/m0../ ...
It was designed to be a weaker antagonist at the neuromuscular junction than pancuronium; hence its monoquaternary structure and its having an allyl group and a pyrrolidine group attached to the D ring quaternary nitrogen atom. Rocuronium has a rapid onset and intermediate duration of action.[2] There is considered to be a risk of allergic reaction to the drug in some patients (particularly those with asthma), but a similar incidence of allergic reactions has been observed by using other members of the same drug class (non-depolarizing neuromuscular blocking drugs).[3] The γ-cyclodextrin derivative sugammadex (trade name Bridion) has been recently introduced as a novel agent to reverse the action of rocuronium.[4] Sugammadex has been in use since 2009 in many European countries; however, it was turned down for approval twice by the US FDA due to concerns over allergic reactions and bleeding,[5] but finally approved the medication for use during surgical procedures in the United States on ...
Glafenine; Quinazolines: Fluproquazone. *Proquazone; Aminonicotinic acids: Clonixeril. *Clonixin. *Flunixin; Sulfonanilides: ...
InChI=1S/C27H33NO10S/c1-12(30)28-16-7-5-13-9-18(37-27-24(34)23(33)22(32)19(11-29)38-27)25(35-2)26(36-3)21(13)14-6-8-20(39-4)17(31)10-15(14)16/h6,8-10,16,19,22-24,27,29,32-34H,5,7,11H2,1-4H3,(H,28,30)/t16-,19+,22+,23-,24+,27+/m0/s1 ...
Sternbach LH, Fryer RI, Keller O, Metlesics W, Sach G, Steiger N (May 1963). "Quinazolines and 1,4-Benzodiazepines. X. Nitro- ...
... (peganine) is a quinazoline alkaloid. It is found in Justicia adhatoda, after which it is named. It is additionally ... Nepali, Kunal; Sharma, Sahil; Ojha, Ritu; Dhar, Kanaya Lal (2012). "Vasicine and structurally related quinazolines". Medicinal ...
... is a heterocyclic chemical compound, a quinazoline with a carbonyl group in the C4N2 ring. Two isomers are ... 2016), "Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities", Res ... 2-Quinazolinone 4-Quinazolinone Common routes to quinazolines involve condensation of amides to anilines with ortho nitrile, ... "Synthesis of quinazolinones and quinazolines". Tetrahedron. 61 (43): 10153-10202. doi:10.1016/j.tet.2005.07.010.. ...
Archer GA, Sternbach LH (1964). "Quinazolines and 1,4-Benzodiazepines. XVI. Synthesis and Transformations of 5-Phenyl-1,4- ...
Walser, A, Zenchoff G (1977). "Quinazolines and 1,4-benzodiazepines. 81. s-Triazolo[4,3-a][1,4]benzodiazepines by oxidative ...
11-Chloro-5-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-2,3-dihydrodiimidazo[1,2-c:1',5'-a]quinazoline ...
8-quinoline > 8-quinazoline > 8-isoquinoline ≥ cinnoline > phthalazine > quinoxaline > 5-quinoline e.g. AMG-517 (fig. 8b), ... quinazoline, phthalazine, quinoxaline, and cinnoline moieties". Journal of Medicinal Chemistry. 48 (3): 744-52. doi:10.1021/ ...
Chemical Encyclopedia: Quinazoline alkaloids. xumuk.ru Aniszewski, p. 106 Aniszewski, p. 105 Richard B. Herbert; Herbert, ...
... is a quinazoline alkaloid. It shows bronchodilatory activity in vitro but bronchoconstrictory activity in vivo. ...
... is a quinazoline derivative. It is a dihydrofolate reductase inhibitor. It has been used with leucovorin in ...
ISBN 978-0122830600 1997: Des Brown & Damon Ridley, Quinazolines. Supplement 1: The Chemistry of Heterocyclic Compounds (Brown ...
Vögtle, Markus M.; Marzinzik, Andreas L. (July 2004). "Synthetic Approaches Towards Quinazolines, Quinazolinones and ...
The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database ...
Quinazolinone Niementowski quinazoline synthesis Armarego, W. L. F. (1963). "Quinazolines". Advances in Heterocyclic Chemistry ... Over 200 biologically active quinazoline and quinoline alkaloids are identified. The synthesis of quinazoline was first ... Quinazoline is an organic compound with the formula C8H6N2. It is an aromatic heterocycle with a bicyclic structure consisting ... Quinazoline protonates (and methylates) at N3. Protonation induces hydration. Many mildly acidic substrates add across the C=N3 ...
Quinazoline derivatives have found applications as anti-malarial agents and in cancer treatment. The presence of a halogen ... Quinazoline is composed of fused benzene and pyrimidine rings. ... quinazoline AldrichCPR C8H3ClFN3O2 * pricing ... Quinazoline is composed of fused benzene and pyrimidine rings. Quinazoline derivatives have found applications as anti-malarial ... quinazoline AldrichCPR C8H4FN3O3 * pricing ...
Quinazoline alkaloids are natural products from the group of alkaloids, which are chemically derived from quinazoline. Some ... quinazolines and indoloquinazolines. Vasicine Evodiamine Rutaecarpine Febrifugine Quinazoline alkaloids can be found mainly in ... About 70 alkaloids with a quinazoline structure are known, which are mostly further classified as simple quinazolinones, ... quinazoline alkaloids show bronchodilatory effects and stimulate respiration. An abortive effect was also found for vasicine in ...
Quinazoline, Alkylquinazolines, and Arylquinazolines.. Halogenoquinazolines.. Oxyquinazolines.. Thioquinazolines.. Nitro, Amino ... Due to the vast increase in the number and types of individual quinazolines described in recent literature, the author has ... replaced the myriad classified tables of known quinazolines with a single alphabetical table of simple known quinazolines. To ... and Related Quinazolines.. Quinazolinecarboxylic Acids and Related Derivatives.. Appendix.. References.. Index. ...
W. L. F. Armarego, A Text Book of Quinazolines, 1963. *R. Rajput and A. P. Mishra, "A review on biological activity of ... I. P. Jung, H. L. So, S. C. Chan, and S. K. Kwan, "Study on the selective reduction of 1H-quinazoline-2,4-diones," Bulletin of ... B. Pati and S. Banerjee, "Quinazolines: an illustrated review," Journal of Advanced Pharmacy. Education & Research, vol. 3, no ... H.-Q. Li, D.-D. Li, X. Lu, Y.-Y. Xu, and H.-L. Zhu, "Design and synthesis of 4,6-substituted-(diaphenylamino)quinazolines as ...
Biotransformation of quinazoline and phthalazine by Aspergillus niger.. [John B Sutherland, Thomas M Heinze, Laura K ... Quinazoline was oxidized to 4-quinazolinone and 2,4-quinazolinedione, and phthalazine was oxidized to 1-phthalazinone. ... Cultures of Aspergillus niger NRRL-599 in fluid Sabouraud medium were grown with quinazoline and phthalazine for 7 days. ...
The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.. Newton R1, ... The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity ... The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity ... The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity ...
... quinazolines. The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step ( ... quinazolines. The imidazoquinazolines were screened for in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells ... quinazolines; cytotoxicity dihalogenated 2H-imidazo[1,2-c]quinazolines; cross-coupling; imidazo[1,2-c]quinazolines; ... Novel Polycarbo-Substituted Imidazo[1,2-c]quinazolines: Synthesis and Cytotoxicity Study. Tebogo Ankie Khoza 1. ...
2WZ6: Structural Discovery of Small Molecule Binding Sites in Cu-Zn Human Superoxide Dismutase Familial Amyotrophic Lateral Sclerosis Mutants Provides Insights for Lead Optimization.
A compound of formula (I) wherein A, X, Y, Z, R.sub.1 and R.sub.24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I.sub.Kur-associated disorders, and other disorders mediated by ion channel function. ##STR00001##
... quinazolines. The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step ( ... quinazolines. The imidazoquinazolines were screened for in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells ... quinazolines; cytotoxicity dihalogenated 2H-imidazo[1,2-c]quinazolines; cross-coupling; imidazo[1,2-c]quinazolines; ... In Vitro Cytotoxicity of Imidazo[1,2-c]quinazolines 3-6. Twenty two (22) of the imidazo[1,2-c]quinazolines were evaluated for ...
For example, reaction of 2-chloro-4-(4-methylpiperazin-1-yl)quinazoline with N-methyl-4-chlorobenzenesulfonamide gave II in 10 ... quinazoline piperazinyl benzenesulfonamide prepn 5HT6 modulator, Alzheimer schizophrenia obesity Parkinson disease treatment ...
Substituted quinazolines of the formula (1): ##STR1## wherein: R 1 to R 4 are independently H, halo, (C 1 -C 4 ) alkyl, ... C07D239/72-Quinazolines; Hydrogenated quinazolines * C07D239/74-Quinazolines; Hydrogenated quinazolines with only hydrogen ... C07D239/72-Quinazolines; Hydrogenated quinazolines * C07D239/86-Quinazolines; Hydrogenated quinazolines with hetero atoms ... C07D239/72-Quinazolines; Hydrogenated quinazolines * C07D239/86-Quinazolines; Hydrogenated quinazolines with hetero atoms ...
A quinazoline compound represented by the general formula (I) or a pharmacologically acceptable salt thereof: ##STR1## (wherein ... It relates to a quinazoline compound useful as a medicine exhibiting an inhibitory action on calmodulin-dependent cGMP-PDE. ... C07D239/72-Quinazolines; Hydrogenated quinazolines * C07D239/86-Quinazolines; Hydrogenated quinazolines with hetero atoms ... Process for preparing quinazolines JPS53103484A (en) * 1977-02-21. 1978-09-08. Takeda Chem Ind Ltd. Quinazoline derivatives, ...
Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C.. Zeng, M., Lu, J., Li, L., Feru, F., Quan, C., Gero, T.W., ... KRAS G12C in bound to quinazoline based switch II pocket (SWIIP) binder. *DOI: 10.2210/pdb5V9L/pdb ... Notably we find that adding an amide substituent to the quinazoline scaffold allows additional interactions with KRAS G12C, and ... Optimized lead compounds in the quinazoline series selectively inhibit KRAS G12C-dependent signaling and cancer cell growth at ...
These treatment failures proved to be due to emergence of parasites resistant to the quinazolines. ... each of these quinazolines effected cure of infections with the Oak Knoll strain at a remarkably small daily dose. However, ... suggesting that the activities of these quinazolines, like those of 6-amino-substituted derivatives, were compromised by ... Studies on the 2,4-Diamino-6-Substituted Quinazolines II. Activities of Selected Derivatives against Infections with Various ...
Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives F. Hu, X. Cui, G. Lu and G. Huang, Org. Biomol. Chem., ...
For the uses and biological importance of benzothia-zole and quinazoline derivatives, see: Schwartz et al. (1992. ); Wolfe et ... In the title compound, C14H10N2O2S, the benzothia-zole and quinazoline ring systems are essentially planar with maximum ... The quinazoline ring system is also essentially planar with the maximum deviation of -0.1588 (15)Å for the N1 atom. The ... For the uses and biological importance of benzothiazole and quinazoline derivatives, see: Schwartz et al. (1992); Wolfe et al. ...
Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for ... Antipsychotic Potential of Quinazoline ErbB1 Inhibitors in a Schizophrenia Model Established With Neonatal Hippocampal ... These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel ...
Design and synthesis of quinazoline derivatives as potential anticancer agents. Ming-Hsieh Chuang, Meng-Ling Chen, Ji-Wang ... Design and synthesis of quinazoline derivatives as potential anticancer agents. Ming-Hsieh Chuang, Meng-Ling Chen, Ji-Wang ... Design and synthesis of quinazoline derivatives as potential anticancer agents. Ming-Hsieh Chuang, Meng-Ling Chen, Ji-Wang ... Design and synthesis of quinazoline derivatives as potential anticancer agents Message Subject (Your Name) has forwarded a page ...
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I ##STR00001## wherein Ar, R.sup.1 ... C. for 1.5 h. After cooling to RT the solvent is evaporated giving rise to crude 4,5-dichloro-7-iodo-quinazoline. To a mixture ... STR00065## 4,5,7-substituted quinazolines of the general formula 3-4, wherein X, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as ... Sulfoximine substituted quinazolines for pharmaceutical compositions Abstract. This invention relates to novel sulfoximine ...
JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles.
... a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised analogues were evaluated against ... Novel amide analogues of quinazoline carboxylate display selective antiproliferative activity and potent EGFR inhibition. *. ... AbstractIn the present study, a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised ... The current investigation could be extremely helpful for the development of newer therapeutically useful quinazoline based ...
Buy Quinazoline (CAS 253-82-7), a specialty product for proteomics research, from Santa Cruz. Molecular Formula: C8H6N2, ... Quinazoline (CAS 253-82-7) *bvseo_sdk, java_sdk, bvseo-3.2.0 ...
Quinazoline is a heterocycle and is, for example, a subunit of many anti-cancer drugs. Up to now, the synthesis of quinazoline ... Like Dominoes: Metal-Free Synthesis of Quinazolines News May 03, 2017 , Original Story from the Friederich-Alexander ... In addition, the novel quinazolines have shown that they are highly effective against herpes viruses, and in contrast to many ... This novel one-pot domino process creates a completely new type of quinazolines, which have intrinsic fluorescence properties. ...
Of 11 quinazolines tested in the secondary assay, 8 quinazolines showed activity superior to doxycycline (Fig. 4F). Members of ... 7 Quinazoline CBR715 demonstrates antiwolbachial efficacy in mouse models of B. malayi and O. ochengi filarial infection.. (A) ... 6 Quinazolines demonstrate antiwolbachial efficacy in mouse model of L. sigmodontis filarial infection.. (A and B) Advanced ... Advanced quinazoline lead eliminates Wolbachia in B. malayi and Onchocerca adult worms in vivo. Because of the demonstrated ...
... quinazolines of the formula: ##STR1## wherein R is (1-pyrrolidinyl)propyl; 3-[bis-(2-hydroxyethyl)amino]propyl; 2,3- ... A mixture of 45 g. (0.145 mole) of 4-chloro-2-(3,4-dichlorophenyl)quinazoline and 44 g. (0.3 mole) of 1-amino-3-diethylamino-2- ... A mixture of 46.5 g. (0.15 mole) of 4-chloro-2-(3,4-dichlorophenyl)quinazoline in 500 ml of dimethylformamide and 29 g (0.31 ... 2-(3,4-Dichlorophenyl)-4-(substituted amino)-quinazolines Abstract. A series of 2-(3,4-dichlorophenyl)-4-(substituted amino) ...
Quinazoline-4(3H) is one of the most frequently encountered heterocycles in medicinal chemistry, which contains a pyrimidine ... Hence in view of the analytical and biological importance of quinazoline-4(3H) and as a part of our continued work on the ... Previously it was reported that quinazoline-4-(3H)-one derivatives have interesting antimicrobial activity against different ... N-Donor Environment of Quinazoline-4(3H)-one Schiff Base and Their Biological Studies,. The Scientific World Journal,. vol. ...
  • Quinazoline derivatives have found applications as anti-malarial agents and in cancer treatment. (sigmaaldrich.com)
  • Though the parent quinazoline molecule is rarely mentioned by itself in technical literature, substituted derivatives have been synthesized for medicinal purposes such as antimalarial and anticancer agents. (wikipedia.org)
  • 7. 2- and 4-halo derivatives of quinazoline undergo displacement by nucleophiles, such as piperidine. (wikipedia.org)
  • A. K. Mahato, B. Srivastava, and S. Nithya, "Chemistry structure activity relationship and biological activity of quinazoline-4(3 H )-one derivatives," Inventi Rapid: MedChem , vol. 2, no. 1, 2011. (hindawi.com)
  • Quinazoline derivatives and pharmacological activities: a review," International Journal of Medicinal Chemistry & Analysis , vol. 3, no. 1, pp. 10-21, 2013. (hindawi.com)
  • Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors," Bioorganic and Medicinal Chemistry Letters , vol. 19, no. 8, pp. 2277-2281, 2009. (hindawi.com)
  • Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation, part 4: structure-activity relationships for substituents on the quinazoline moiety of 4-[4-(N-substituted(thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives," Bioorganic and Medicinal Chemistry Letters , vol. 13, no. 18, pp. 3001-3004, 2003. (hindawi.com)
  • However, doses required for cure of infections with the Camp-CH/Q strain were from 4-48 times those required for cure of infections with the Oak Knoll strain, suggesting that the activities of these quinazolines, like those of 6-amino-substituted derivatives, were compromised by pyrimethamine resistance. (ajtmh.org)
  • Quinazoline derivatives have been reported to possess various biological activities. (aacrjournals.org)
  • Thus, the methoxy group was introduced onto quinazoline derivatives at the 6- and 7-position to expect better inhibitory activity. (aacrjournals.org)
  • AbstractIn the present study, a novel series of quinazoline derivatives is developed for cancer therapy. (medworm.com)
  • Previously it was reported that quinazoline-4-(3H)-one derivatives have interesting antimicrobial activity against different species of gram-positive, gram-negative, and pathogenic fungi [ 4 ]. (hindawi.com)
  • In addition, many substituted quinazoline derivatives have recently earned great interest in chemotherapy as antitumor drugs [ 8 ]. (hindawi.com)
  • The book entitled "Triazolo Quinazolines: Synthesis and Biological Prediction Study" includes a comprehensive review of MW reactions and the Synthesis, Characterization and Biological Prediction Study of Triazolo Quinazoline Derivatives. (morebooks.de)
  • In the present study, we evaluated cytotoxic effects of various styrylquinazoline derivatives and found that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ) most potently inhibited the proliferation of the human cervical carcinoma HeLa cells. (spandidos-publications.com)
  • Many quinazoline derivatives were reported to have potent cytotoxic activity. (eurekaselect.com)
  • Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. (eurekaselect.com)
  • Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. (eurekaselect.com)
  • Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease. (eurekaselect.com)
  • Gholami, Milad 2013-11-30 00:00:00 A simple and facile synthesis of highly functionalized quinazoline derivatives has been successfully developed by treatment of aldehydes, ammonium acetate, and 2-aminoaryl ketones or isatoic anhydride under reflux conditions in the presence of a pentafluorophenylammonium triflate (PFPAT) organocatalyst. (deepdyve.com)
  • We developed a straightforward method for making isatoic anhydride-8-amide from isatin-7-carboxylic acid as a tool to easily produce a range of quinazoline and substituted aniline derivatives using adaptable pH-sensitive cyclization chemistry. (elsevier.com)
  • The approaches are inexpensive, simple, fast, efficient at room temperature and scalable, enabling the synthesis of both established and new quinazolines and also highly substituted anilines including cyano derivatives. (elsevier.com)
  • Materials and Methods: A dataset of 47 analogues of pyrazolo quinazolines were selected with their inhibitory activity on CDK2/Cyclin A. The derivatives were divided into training and test sets. (elsevier.com)
  • The present invention relates to quinazoline derivatives, which are useful as medicaments, particularly antipruritic agents, or salts thereof and pharmaceutical compositions containing any of them as active ingredients. (justia.com)
  • The synthesis of a series of push-pull arylvinyl (styryl), aryl, and arylethynyl quinazoline derivatives by means of different straightforward protocols is reported. (archives-ouvertes.fr)
  • Electrotopological state indices for atomtype (ETSIAT)were employed to establish a quantitative structure- activity relationship (QSAR) model of antitumor activity for 17 indolo[1,2-b]quinazoline derivatives. (pku.edu.cn)
  • N=, -NH-, =O, and >N- were closely correlated with the antitumor activities of indol[1,2-b]quinazoline derivatives. (pku.edu.cn)
  • Prediction of Antitumor Activities of Indolo[1,2-b]Quinazoline Derivatives Using Electrotopological State Indices for AtomTypes[J].Acta Phys. (pku.edu.cn)
  • Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2," Bioorganic and Medicinal Chemistry , vol. 15, no. 11, pp. 3635-3648, 2007. (hindawi.com)
  • Identification of 4-piperazin-1-yl-quinazoline template based aryl and benzyl thioureas as potent, selective, and orally bioavailable inhibitors of platelet-derived growth factor (PDGF) receptor," Bioorganic and Medicinal Chemistry Letters , vol. 14, no. 19, pp. 4867-4872, 2004. (hindawi.com)
  • Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: Selective inhibitors of Aurora B kinase with potent anti-tumor activity," Bioorganic and Medicinal Chemistry Letters , vol. 18, no. 6, pp. 1904-1909, 2008. (hindawi.com)
  • The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity. (nih.gov)
  • Notably we find that adding an amide substituent to the quinazoline scaffold allows additional interactions with KRAS G12C, and remarkably increases the labeling efficiency, potency, and selectivity of KRAS G12C inhibitors. (rcsb.org)
  • Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. (go.jp)
  • These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. (go.jp)
  • Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. (eurekaselect.com)
  • Marwa F. Ahmed* and Naja Magdy, "Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity", Anti-Cancer Agents in Medicinal Chemistry (2017) 17: 832. (eurekaselect.com)
  • CB30865 (p-[N-(7-bromo-3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl+ ++)-N-(prop-2-ynyl)amino]-N-(3-pyridylmethyl)benzamide) is a quinazoline-based pyridine-containing compound that emerged from a programme aimed at the development of thymidylate synthase (TS) inhibitors as anticancer agents. (semanticscholar.org)
  • Our study aims on learning the application of five important binary fingerprinting techniques based on the quantum mechanics involving 2D QSAR studies for designing novel pyrazolo quinazolines as selective inhibitors of CDK2/CyclinA. (elsevier.com)
  • Quinazoline scaffold has been successfully utilized for development of various inhibitors of tubulin, epidermal growth factor receptor (EGFR), polo like kinases (PLKs), Hedgehog-Gli signaling pathway and protein kinase B (PKB) /Akt pathway. (elsevier.com)
  • Compounds based on quinazolines have shown efficacies in μM to nM range in various cancer cell lines and thus could be useful scaffolds for development of both apoptosis inducers as well as inhibitors. (elsevier.com)
  • This compilation is based on various patents published till 2015 and divides the quinazolines in two main categories: Quinazolines as apoptosis inducers and as apoptosis inhibitors. (elsevier.com)
  • Over 200 biologically active quinazoline and quinoline alkaloids are identified. (wikipedia.org)
  • Biologically active quinoline and quinazoline alkaloids part I." Medicinal Research Reviews. (wikipedia.org)
  • Quinazoline alkaloids are natural products from the group of alkaloids, which are chemically derived from quinazoline. (wikipedia.org)
  • Some quinazoline alkaloids show bronchodilatory effects and stimulate respiration. (wikipedia.org)
  • About 70 alkaloids with a quinazoline structure are known, which are mostly further classified as simple quinazolinones, pyrroloquinazolines, pyrido[2,1-b]quinazolines and indoloquinazolines. (wikipedia.org)
  • Vasicine Evodiamine Rutaecarpine Febrifugine Quinazoline alkaloids can be found mainly in plants, such as acanthaceae (Adhatoda vasica), rutaceae, saxifragaceae (Dichroa febrifuga) and in linaria species (Scrophulariaceae) and peganum harmala (Fam. (wikipedia.org)
  • The quinazoline moiety is a building block for about 150 naturally occurring alkaloids and drugs. (morebooks.de)
  • A series of quinazoline alkaloids fused with 1,4-benzodiazepinone are isolated from different fungal species or their cultures. (aspeneducationgroup.com)
  • Also known as 1,3-diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. (wikipedia.org)
  • The synthesis of quinazoline was first reported in 1895 by August Bischler and Lang through the decarboxylation of the 2-carboxy derivative (quinazoline-2-carboxylic acid). (wikipedia.org)
  • Anti-tumor effects of B-2, a novel 2,3-disubstituted 8-arylamino-3H-imidazo[4,5-g]quinazoline derivative, on the human lung adenocarcinoma A549 cell line in vitro and in vivo," Chemico-Biological Interactions , vol. 189, no. 1-2, pp. 90-99, 2011. (hindawi.com)
  • The quinazoline derivative PVHD121 has anti-cell proliferative activity and inhibits tubulin polymerization by binding to the colchicine site of tubulin. (aspetjournals.org)
  • We here report a study on the mechanism of action of PVHD121, a quinazoline derivative binding to the colchicine site of tubulin. (aspetjournals.org)
  • Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative). (aspetjournals.org)
  • We investigated the effect of a novel quinazoline derivative (KB-5666), a lipid peroxidation inhibitor, on ischemic neuronal damage using Mongolian gerbils. (aspetjournals.org)
  • The present inventors have found that a quinazoline derivative has a nociceptin antagonism and is useful as an analgesic (see Patent Document 1). (justia.com)
  • Patent Document 2 describes, as a compound having a carbonylamino group at the 2-position of the quinazoline skeleton, a quinazoline derivative that has a neuropeptide Y (NPY) receptor subtype Y5 inhibitory effect and is useful for pain relief and memory disorder. (justia.com)
  • Patent Document 3 describes a quinazoline derivative, which is useful for bone diseases. (justia.com)
  • Patent Document 4 describes a quinazoline derivative, which has a LTB4 (leucotriene B4) antagonism and is useful as an anti-inflammatory. (justia.com)
  • The present invention relates to pyrazolo-quinazolines, characterized by an ortho-substituted-arylamino, heterocyclylamino- or C 3 -C 7 cycloalkylamino residue at 8 position and an aryl, heterocyclyl or C 3 -C 7 cycloalkyl as substituent of a carboxamide at 3 position of the molecula framework. (patentsencyclopedia.com)
  • The present invention relates to fungicidal mixtures, comprising at least one quinazoline compound I and one compound II as defined in the description, and to compositions comprising these mixtures. (patentsencyclopedia.com)
  • The present invention relates to the use of quinazolines of formula (I), wherein the groups Ra to Rd have the meanings given in the claims and specification, in cancer therapy. (justia.com)
  • The two main synthetic approaches towards imidazo[1,2- c ]quinazolines involve either annulation of quinazoline moiety onto an imidazole framework or a two-step assembly of the imidazole ring onto a quinazoline framework. (mdpi.com)
  • The work has been a continuation of our work from the series of seven books namely Pyrimidines, Quinazolines, Pyrimidines fused with heterocyclic rings, Novel Pyrazoles part I and Novel Pyrazoles part II, Triazolo Pyrimidines and Thiazolo Pyrimidines. (morebooks.de)
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  • The peculiarities and differences of 1H- and 13C-NMR spectral patterns of 5-R-2-aryl-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolines and their aromatic analogues have been described. (edu.ua)
  • Imidazo[1,2- c ]quinazoline-based compounds continue to attract attention in synthesis because of their application in pharmaceuticals and materials [ 1 ]. (mdpi.com)
  • We demonstrate that covalent quinazoline-based switch II pocket (SIIP) compounds effectively suppress GTP loading of KRAS G12C, MAPK phosphorylation, and the growth of cancer cells harboring G12C. (rcsb.org)
  • Optimized lead compounds in the quinazoline series selectively inhibit KRAS G12C-dependent signaling and cancer cell growth at sub-micromolar concentrations. (rcsb.org)
  • Up to now, the synthesis of quinazoline heterocycles was very costly and required many individual steps starting with expensive compounds and reagents. (technologynetworks.com)
  • In addition, the novel quinazolines have shown that they are highly effective against herpes viruses, and in contrast to many other bioactive compounds, do not damage healthy cells. (technologynetworks.com)
  • Their synthetic utility was demonstrated by condensation reactions with carbonyl compounds or amines to provide SF 5 -containing quinolines and quinazolines, respectively. (beilstein-journals.org)
  • The promising anticancer profile of some of the quinazoline based compounds clearly highlights the clinical potential of this heterocycle. (elsevier.com)
  • Quinazoline ring systems have a prominent feature in medicinal chemistry and possess biological activities such as antimalarial, anticonvulsant, antibacterial, antidiabetic, and anticancer. (morebooks.de)
  • This review will act as a tool for the researchers working on exploring the anticancer potential of quinazoline as a privileged heterocyclic. (elsevier.com)
  • One-pot reductive cyclization to antitumor quinazoline precursorsOn resonance interactions in methyl 4-X-benzoates and the effect of 2,6-dimethyl substitution. (easechem.com)
  • Quinazoline is composed of fused benzene and pyrimidine rings. (sigmaaldrich.com)
  • This paper presents a first quantitative kinetic model for supercritical water oxidation (SCWO) of quinazoline that describes the formation and interconversion of intermediates and final products at 673-873 K. The set of 11 reaction pathways for phenol, pyrimidine, naphthalene, NH3, etc, involved in the simplified reaction network proved sufficient for fitting the experimental results satisfactorily. (usda.gov)
  • The pyrimidine yielding from quinazoline is the dominant ring-opening pathway and provides a significant contribution to CO2 formation. (usda.gov)
  • Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions. (technologynetworks.com)
  • They have developed a novel synthetic route towards antiviral quinazoline heterocycles that have not been described previously in professional literature. (technologynetworks.com)
  • Cell cycle effects of CB30865, a lipophilic quinazoline-based analogue of the antifolate thymidylate synthase inhibitor ICI 198583 with an undefined mechanism of action. (semanticscholar.org)
  • Quinazolinone Niementowski quinazoline synthesis Armarego, W. L. F. (1963). (wikipedia.org)
  • W. L. F. Armarego, A Text Book of Quinazolines , 1963. (hindawi.com)
  • Quinazoline is an organic compound with the formula C8H6N2. (wikipedia.org)
  • In the title compound, C 14 H 10 N 2 O 2 S, the benzothia-zole and quinazoline ring systems are essentially planar with maximum deviations of 0.0127 (16) and 0.1588 (15) Å, respectively, and make a dihedral angleof 3.02 (5)°, which shows that the entire mol-ecule is almost planar. (iucr.org)
  • The title compound comprises a benzothiazole ring fused with quinazoline ring. (iucr.org)
  • The thiazole ring (C1/C6/C7/N1/S1) forms a dihedral angle of 0.34 (8)° and 3.15 (6)° with the phenyl ring (C1-C6) and the quinazoline ring system, respectively. (iucr.org)
  • The results of the comprehensive structure-activity relationship study confirmed the assumption that two or more electronegative groups on the phenyl ring attached to the thiazolo[2,3-b]quinazoline system showed the optimum effect. (dovepress.com)
  • The aldonitrone 1c also reacts with N-methylmaleimide and with phenyl vinyl sulfone to furnish the first examples of primary cycloaddition products from quinazoline 3-oxides. (nuigalway.ie)
  • In such fashion, in this paper, we report the synthesis and anticonvulsant activity (Chemo shock) of N-1(substituted-N-4[(4-oxo-3-phenyl-3, 4-dihydro-quinazoline-2-ylmethyl) semicarbazones 3A-d (1-7), 3B-d (1-7), 3C-d (1-7), their chemical structure were characterized using IR, H-H NMR, and elemental analysis techniques. (innovareacademics.in)
  • Nitro, Amino, and Related Quinazolines. (wiley.com)
  • Amination of the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines with 2-aminoethanol followed by acid-promoted cyclodehydration of the incipient 2-((6,8-dihalo-2-phenylquinazolin-4-yl)amino)ethanols afforded the corresponding novel 5-aryl-9-bromo-7-iodo-2,3-dihydro-2 H -imidazo[1,2- c ]quinazolines. (mdpi.com)
  • The ''Global and Chinese 4-amino-2-chloro-6,7-dimethoxy quinazoline Industry, 2011-2021 Market Research Report'' is a professional and in-depth study on the current state of the global 4-amino-2-chloro-6,7-dimethoxy quinazoline industry with a focus on the Chinese market. (reportsnreports.com)
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  • Through the statistical analysis, the report depicts the global and Chinese total market of 4-amino-2-chloro-6,7-dimethoxy quinazoline industry including capacity, production, production value, cost/profit, supply/demand and Chinese import/export. (reportsnreports.com)
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  • Overall, the report provides an in-depth insight of 2011-2021 global and Chinese 4-amino-2-chloro-6,7-dimethoxy quinazoline industry covering all important parameters. (reportsnreports.com)
  • 5.2 Market Competition of 4-amino-2-chloro-6,7-dimethoxy quinazoline Industry by Country (USA, EU, Japan, Chinese etc. (reportsnreports.com)
  • The optimal conditions of the reaction have been found, and factors contributing to oxidation of 5-R-2-aryl-5,6-dihydro-[1,2,4]triazolo[1,5-с]quinazolines have been determined. (edu.ua)
  • The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step (Sonogashira/Stille) cross-coupling reactions to afford diversely functionalized polycarbo-substituted 2 H -imidazo[1,2- c ]quinazolines. (mdpi.com)
  • The iridium and platinum cyclometalated imidazo[1,2- c ]quinazolines have also been patented as efficient dopants for organic electroluminescent layers in organic light emitting diodes (OLEDS) [ 6 ]. (mdpi.com)
  • The current investigation could be extremely helpful for the development of newer therapeutically useful quinazoline based molecules for cancer therapy. (medworm.com)
  • The reaction proceeded smoothly under metal-free conditions, which provided quinazoline-containing heterocyclic molecules in moderate to good yields. (rsc.org)
  • Biotransformation of quinazoline and phthalazine by Aspergillus niger. (sigmaaldrich.com)
  • Cultures of Aspergillus niger NRRL-599 in fluid Sabouraud medium were grown with quinazoline and phthalazine for 7 days. (sigmaaldrich.com)
  • Biological Activities of the Alkaloid Quinazoline Extracted from Aspergillus nomius ', Egyptian Journal of Botany , 57(3), pp. 565-582. (ekb.eg)
  • Quinazoline was oxidized to 4-quinazolinone and 2,4-quinazolinedione, and phthalazine was oxidized to 1-phthalazinone. (sigmaaldrich.com)
  • Structural studies using X-ray crystallography reveal a new conformation of SIIP and key interactions made by substituents located at the quinazoline 2-, 4-, and 7-positions. (rcsb.org)
  • In 1903, Siegmund Gabriel reported the synthesis of the parent quinazoline from o-nitrobenzylamine, which was reduced with hydrogen iodide and red phosphorus to 2-aminobenzylamine. (wikipedia.org)
  • For example, reaction of 2-chloro-4-(4-methylpiperazin-1-yl)quinazoline with N-methyl-4-chlorobenzenesulfonamide gave II in 10% yield. (diva-portal.org)
  • Quinazoline is a planar molecule. (wikipedia.org)
  • The quinazoline ring system is also essentially planar with the maximum deviation of -0.1588 (15)Å for the N1 atom. (iucr.org)
  • The 5-(4-chlorostyryl)-2-phenylimidazo[1,2- c ] quinazoline 2 , on the other hand, was found to exhibit significant anti-cancer activity against HEP-G2 liver cell line [ 5 ]. (mdpi.com)
  • Quinazoline is a heterocycle and is, for example, a subunit of many anti-cancer drugs. (technologynetworks.com)
  • A series of new 2, 4-disubstituted quinazolines were synthesized by an analog design approach. (bvsalud.org)
  • Quinazoline-containing drugs Gefitinib for treatment of non-small-cell lung carcinoma. (wikipedia.org)
  • As compared with the doses of standard drugs required for cure of infections with drug-susceptible strains or doses of the newly developed aminoalcohols required for cure of either drug-susceptible or drug-resistant strains, each of these quinazolines effected cure of infections with the Oak Knoll strain at a remarkably small daily dose. (ajtmh.org)