Therapeutic agents family protein kinase inhibitors. Medical search. Frequent questions

Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. (haematologica.org)
Some of Cyclacel's foundational work involved experiments that determined that the combination of cyclin-dependent kinase 2 (CDK 2) and CDK 9 inhibitors is more powerful in blocking the cell cycle than independent administration of either molecule. (scienceboard.net)
Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. (endocrine-abstracts.org)

Breast cancer therapy has improved following the development of drugs with specific molecular targets, exemplified by inhibitors of human epidermal growth factor receptor-2 (HER2) or epidermal growth factor receptor (EGFR) such as trastuzumab and lapatinib. (jcancer.org)
The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
This family, which includes epidermal growth factor receptor (EGFR), plays a pivotal role in normal cell growth, lineage determination, repair, and functional differentiation. (medscape.com)
Receptor tyrosine kinase inhibitors targeting FLT3 have developed as attractive treatment options. (ashpublications.org)
FLT3 (FMS-like tyrosine kinase 3) is a type III receptor tyrosine kinase (RTK) closely related to the platelet-derived growth factor (PDGF) receptor and c-Kit with important functions in the regulation of early hematopoietic cells. (ashpublications.org)
Activity of these inhibitors depends on their mechanism of receptor binding (active vs inactive conformation) and efficacy against the FLT3-ITD and -TKD mutations (type 1 inhibitors are active both on FLT3 -ITD and TKD, whereas type 2 inhibitors are active only on FLT3 -ITD). (dovepress.com)
MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. (frontiersin.org)
solid course="kwd-title" Keywords: G protein-coupled receptor (GPCR), a desintegrin and metalloprotease (ADAM), transactivation, growth factor receptor 1. (exposed-skin-care.net)
In lots of tumor cells these inter-receptor communications have already been from the resistance to tyrosine kinase inhibitors [18]. (exposed-skin-care.net)
Both receptors belong to the TAM (TYRO3, AXL and MER - MER proto-oncogene, tyrosine kinase) receptor tyrosine kinase family, which emerged as new potential targets in many oncological diseases, from leukaemia to solid tumours ( Graham et al, 2014 ). (nature.com)
13 , 14 However, the amino acid perfectly maintains the stability of the mutual structural conformation of the virus S-protein and the ACE2 receptor in a holistic manner. (medsci.org)
The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. (bmj.com)
Alterations in receptor tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1, include overexpression, amplification or mutations. (bmj.com)
Novel therapeutic agents, in particular those that specifically target members of the human epidermal growth factor receptor (HER (ErbB1)) pathway, have shown encouraging therapeutic efficacy. (bmj.com)

We investigated the effects of TAK-285, a novel, investigational, dual EGFR/HER2 inhibitor that has been shown to penetrate the CNS and has comparable inhibitory efficacy to lapatinib which is a known Pgp substrate. (jcancer.org)
Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
Furthermore, GPCR-ligands [15,18] and cytokines such as for example growth hormones (GH) and prolactin (PRL) [19] have the ability to phosphorylate the EGFR in the lack of EGFR-ligand shedding upon the activation of Src and Janus tyrosine kinase 1 (Jak1), respectively. (exposed-skin-care.net)
EGFR represents a rational target for anti-tumor strategies, however anti-EGFR agents show no effective response in HCC patients [20,21]. (exposed-skin-care.net)
Indeed as Efaproxiral stated before, EGFR transactivation may Efaproxiral thus represent a fresh therapeutic target [15,22]. (exposed-skin-care.net)
2.?The EGFR System EGFR, also called ErbB1/HER1, is a 170 kDa transmembrane glycoprotein that defines a family group of tyrosine kinase. (exposed-skin-care.net)
3 The development of molecular targeted therapies aimed at these molecular alterations has generated great optimism for the treatment of cancers such as NSCLC, and drugs targeting the EGFR tyrosine kinase domain are now available. (bmj.com)

Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. (medscape.com)
Various techniques have been developed for targeting cancer cells: gene therapy, monoclonal antibodies (MAbs), antibody toxin conjugates, small-molecule inhibitors, antisense molecules, and tumor vaccines. (medscape.com)
Some are focusing on small-molecule inhibitors for identifying and targeting key kinases that hamper T-cell responses to tumor cells. (genengnews.com)
It exhibits potent antitumor activity by activating tumor-infiltrating CD8 + and CD4 + T cells and has a better therapeutic window relative to recombinant human IL-2. (genengnews.com)
Therapeutic approaches that target the metabolism of tumor cells have been a popular research topic in recent years. (spandidos-publications.com)
Growing evidence suggests that the interaction between the genomic/epigenomic aberrations in cancer cells and the surrounding microenvironment, composed of immune and stromal cells, contributes to the development of tumor invasion via mechanisms such as the so-called "angiogenic switch,"[3-5] creating multiple opportunities for therapeutic intervention. (cancernetwork.com)
LKB1 is a serine/threonine kinase mutated in Peutz-Jeghers syndrome (PJS), implicated in many cellular processes including energy metabolism, cell polarization and cell cycle arrest and has also been shown to play an essential role as a tumor suppressor gene by negatively regulating the mTOR pathway. (scirp.org)
Both glutathione S-transferase pi ( GSTpi ) (80%, 24/30 in tumor and 56.7%, 17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) ( CFTR ) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. (wjgnet.com)
These precision medicine approaches use next-generation sequencing and liquid biopsy to identify tumor cells and actionable protein targets from noninvasive patient samples. (scienceboard.net)
Protein kinase C (PKC) is a key enzyme which regulates proliferation, apoptosis and differentiation, representing a pharmacological target for tumor therapy. (endocrine-abstracts.org)
Targeted' therapy starts with the discovery of a protein that is expressed on the surface of tumor cells but not (or in a limited way) in normal human tissues. (sarcomahelp.org)
By inhibiting this protein they expect to be able to inhibit tumor growth. (sarcomahelp.org)
The third protein involved in the study, CSF1 , is not expressed on the cell surface but instead is secreted by the tumor cells into the surrounding environment. (sarcomahelp.org)
After secretion by the tumor cells, the CSF1 protein attracts macrophages and these macrophages can help the tumor to grow by helping to provide new blood vessels for the tumor. (sarcomahelp.org)
This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)

Most antineoplastic agents have limited access to the central nervous system (CNS) following systemic administration. (jcancer.org)
These transport systems are responsible for the rapid removal of therapeutic agents from the CNS following local or systemic administration and thus contribute to relatively ineffective concentrations in the brain that characterize many antineoplastic agents. (jcancer.org)

Moreover, we highlight the potential therapeutic targets of cellular senescence in diabetic nephropathy and provide important clues for clinical strategies. (hindawi.com)
Furthermore, we will explore the potential therapeutic targets of cellular senescence and provide important clues for clinical strategies in the management of DN. (hindawi.com)
Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. (frontiersin.org)
Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. (frontiersin.org)
Within the last years the detailed characterization of critical molecular pathways implicated in the pathogenesis of HCC has uncovered therapeutic targets that are being explored because of their effectiveness in the prevention and treatment of HCC [3,4]. (exposed-skin-care.net)
In this two-year study, Dr. van de Rijn and Santosh Gupta, PhD aim to determine whether three proteins that are expressed at various levels in LMS tumors can be used as targets for novel therapies. (sarcomahelp.org)
3 Syk-catalyzed phosphorylation mediates interactions between the Fcε receptors and their downstream targets, and Syk is one of several kinases implicated in this allergic cascade. (reviewofophthalmology.com)
At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. (cdc.gov)

This transactivation could be triggered by multiple G-protein coupled receptors (GPCRs), cytokine receptors, integrins and other tyrosine kinase receptors (TKRs) [13-15]. (exposed-skin-care.net)

We explore the pipeline of Akt inhibitors and their preclinical and clinical examination status, presenting the potential clinical application of these agents as a monotherapy or in combination with ionizing radiation, other targeted therapies, or chemotherapy. (spandidos-publications.com)
These events are influenced by and activate other molecular pathways, including phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK),[2] and therapies are now available that target these pathocellular processes. (cancernetwork.com)
But Rombotis explained that the industry now has far more sophisticated tools (i.e., genetic profiling to identify elevated proteins) to guide the development and treatment of targeted small-molecule therapies. (scienceboard.net)
Applying "drug target constellation" (DTECT) mapping, we further show that protein levels of TTF1 and cMYC predict response to targeted therapies including aurora kinase, Bcl2, and HSP90 inhibitors. (oncotarget.com)
His research on CML, including the development of the first animal model of the disease, later contributed to the development of molecularly targeted drug therapies such as imatinib that inhibit the abnormal protein. (cml-foundation.org)
Perhaps most importantly, we will investigate the interplay between therapies directed at each of these proteins. (sarcomahelp.org)
Dr. van de Rijn hopes that it will be possible to combine therapies that target different LMS proteins in order to maximize their effectiveness: 'Perhaps most importantly, we will investigate the interplay between therapies directed at each of these proteins. (sarcomahelp.org)
Syk inhibitors have been touted as potential therapies for leukemias and lymphomas, for autoimmune and allergic asthma conditions, and for allergies. (reviewofophthalmology.com)
Like Syk, other kinase inhibitors have the potential to be useful therapies for ocular allergy. (reviewofophthalmology.com)
The development of targeted therapies has also been followed by resistance, reminiscent of an evolutionary arms race, as exemplified by imatinib and other BCR-ABL inhibitors for the treatment of chronic myelogenous leukaemia. (nature.com)

Ku70/80 forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK [7]. (termedia.pl)
This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)

The binding of these inhibitors blocks the Bcr-Abl kinase in the inactive conformation and provides an advantage in overcoming drug resistance due to kinase mutations. (eurekaselect.com)
Scope includes mutations and abnormal protein expression. (cancerindex.org)
Constitutively activating internal tandem duplications (ITD) of FLT3 (FMS-like tyrosine kinase 3) are the most common mutations in acute myeloid leukemia (AML) and correlate with poor prognosis. (ashpublications.org)
PKC412 is one of several FLT3 inhibitors that is currently evaluated in late-stage clinical trials in AML patients carrying FLT3 mutations. (ashpublications.org)
A spectacular example of this approach to treatment of breast cancer is application of a poly (ADP-ribose) polymerase (PARP) inhibitor, such as olaparib, to patients with germline BRCA1 mutations [4, 5]. (termedia.pl)
There are only a few reports on the expression of Ku70/80 in breast cancers [17-21], but the association of this protein with germline CHEK2 mutations in breast cancer patients is unknown. (termedia.pl)
The treatment paradigm of AML patients harboring FLT3 mutations (30%) has been modified by the discovery of tyrosine kinase inhibitors. (dovepress.com)

The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (cancerindex.org)

Because relapses occur after initial responses, identification of FLT3-ITD-mediated signaling events are important to facilitate novel therapeutic interventions. (ashpublications.org)

Key drug efflux transporters operational in preserving the BBB are the P-glycoprotein (Pgp) transporter, which belongs to the ATP-binding cassette (ABC) transporter family, and the breast cancer resistance protein (BCRP) ABCG2 ( 4 , 5 ). (jcancer.org)
The T315I mutation at the gatekeeper residue is very frequent in advanced phases of the disease and is one of the main causes of resistance, disrupting important contact points between the inhibitors and the enzyme. (eurekaselect.com)
Different strategies have been implemented to overcome this resistance, such as the recent development of more selective non-ATP competitive inhibitors targeting sites outside the ATP-binding cleft. (eurekaselect.com)
PGP inhibitors are being developed to overcome multidrug resistance and two that have reached clinical trials are varapamil, a calcium channel blocker, and cyclosporin A, an immunosuppressant [7]. (savedelicious.com)
The actual resistance level regarding IM-9R cellular traces, MDR-1 phrase and also features, equity level of responsiveness and Bcl-2 and caspases health proteins appearance are usually assessed. (azd5582inhibitor.com)
Fadra can be administered as a second- or third-line therapy to target resistance proteins, suppress them, and delay or prevent relapse. (scienceboard.net)
Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/pan-erb inhibitors. (bmj.com)
Since then, chemotherapy has been one of the main therapeutic strategies in cancer treatment, but, to paraphrase Paul Ehrlich, resistance has followed as a faithful shadow. (nature.com)
The cytochrome P 450 enzymes, a multigene family of constitutive and inducible haem-containing oxidative enzymes from the liver, play an important role in the metabolism of a diverse range of xenobiotics and are often overexpressed in a variety of solid tumours in which they can contribute to drug resistance. (nature.com)
Many anticancer drugs, such as platinum compounds, alkylating agents and nitrosoureas, cause direct damage to the structural integrity of the DNA, and resistance to these compounds results from activation of DNA repair systems. (nature.com)
We also synthesize a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes which, upon activation, confer resistance to a BRAF inhibitor. (cdc.gov)

Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. (nih.gov)

Among the currently available options for the treatment of chronic myeloid leukemia (CML), ATP-competitive tyrosine kinases inhibitors (Gleevec ® , Dasatinib ® and Nilotinib ® ) represent one of the most promising therapeutic approaches developed in the last 10-15 years. (eurekaselect.com)
An example of such a targeted therapy can be found in GIST, where the KIT protein is expressed on almost all GIST tumors and where this protein can be inhibited by Gleevec. (sarcomahelp.org)
A recently published study found the long sought after bridge between mast cells and asthma by demonstrating the positive effects of imatinib (Gleevec, Novartis), a kinase inhibitor currently approved for treatment of chronic myeloid leukemias and stromal tumors. (reviewofophthalmology.com)

The Company's pipeline also includes pimasertib, an investigational, oral, highly-selective small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2). (itbusinessnet.com)
Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. (frontiersin.org)

Tested against a panel of 96 kinases, TAK-285 showed specificity for inhibition of HER family kinases. (jcancer.org)
Similar findings were made in bone marrow cells from gene-targeted mice lacking Bim and/or Puma infected with FLT3-ITD and treated with inhibitor, where loss of Puma only provided transient protection from apoptosis, but loss of Bim preserved clonal survival upon FLT3-ITD inhibition. (ashpublications.org)
In addition, other PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor combination checkpoint inhibition regimens that are presently in clinical trials include atezolizumab (anti-PD-L1 MoAb) plus ipilimumab, pembrolizumab (IgG4 anti-PD-1 MoAb) plus ipilimumab, and tremelimumab (IgG2 anti-CTLA-4 MoAb) plus durvalumab (Fc optimized anti-PD-L1 MoAb) [ 10 ]. (biomedcentral.com)

Arcaro A and Guerreiro AS: The phosphoinositide 3-kinase pathway in human cancer: Genetic alterations and therapeutic implications. (spandidos-publications.com)
Inactivation of the PI3-kinase pathway, but not of Ras-mitogen-activated protein (MAP) kinase signaling, was essential to elicit cytotoxic responses. (ashpublications.org)
Previous studies have demonstrated that glycolysis inhibitors reduce the proliferation of non‑small cell lung cancer (NSCLC) cells by interfering with the aerobic glycolytic pathway. (spandidos-publications.com)
It has been reported that lung cancer cells exhibit upregulated expression of all key glycolytic enzymes [hexokinase 2 (HK2), phosphofructokinase and pyruvate kinase (PK)] ( 13 ), suggesting that the essential enzymes of the aerobic glycolytic pathway have a critical role in the development of lung carcinoma. (spandidos-publications.com)
Another kinase in the crosshairs is IkK-β, a component in the NFκB gene regulatory pathway. (reviewofophthalmology.com)

Our previous study has shown that CCAAT-enhancer binding protein β (C/EBPβ) is an important regulator in METH-induced neuronal autophagy and apoptosis. (cancerindex.org)

For animals in pre-clinical trials, Therapeutic Index = L D 50 E D 50 {\displaystyle {\text{Therapeutic Index}}=\mathrm {\frac {LD_{50}}{ED_{50}}} } For humans in clinical trials, Therapeutic Index = T D 50 E D 50 {\displaystyle {\text{Therapeutic Index}}=\mathrm {\frac {TD_{50}}{ED_{50}}} } For many drugs, severe toxicities in humans occur at sublethal doses, which limit their maximum dose. (wikipedia.org)
Metformin, a known inhibitor of mitochondrial OXPHOS, has been indicated to reduce NSCLC morbidity and mortality in clinical studies. (spandidos-publications.com)
The present article reviewed the therapeutic effects of metformin against NSCLC, both as a single agent and combined with other anticancer treatments, in order to provide a theoretical basis for its clinical use in adjuvant therapy for NSCLC. (spandidos-publications.com)
Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens. (biomedcentral.com)
Based on substantial pre-clinical and clinical evidence, several immunotherapy agents have received approval by the FDA as standard of care treatment for various malignancies over the past two decades [ 1 , 2 ]. (biomedcentral.com)
Recent evidence suggests that the combined use of an anti-CTLA-4 immune-checkpoint inhibitor with an anti-PD-1/PD-L1 MoAb may have complementary action, thus yielding a higher clinical efficacy than either agent individually [ 6 , 7 ]. (biomedcentral.com)
Comprehensive data on the efficacy of MoAb combination therapy in clinical settings is warranted in order to ascertain the true therapeutic value of this treatment strategy. (biomedcentral.com)
Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. (itbusinessnet.com)
Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS. (nature.com)

Magmas, a gene encoding for the mitochondrial import inner membrane translocase subunit, Tim16, protects different cell lines from the antitumoral effects of several pro-apoptotic stimuli (i.e. chemicals and chemotherapeutic agents). (endocrine-abstracts.org)

BACKGROUND: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. (bvsalud.org)

The exact biological mechanism(s) by which the BBB limits drug exposure is not clear, but in addition to epithelial tight junctions, enhanced efflux of chemotherapeutic agents out of the CNS space by endothelial cell membrane transporters in brain blood vessels plays a primary role ( 2 ). (jcancer.org)
The remainder of this review will focus on the different chemotherapeutic agents currently being used for the treatment of cancer and their mechanism of action. (savedelicious.com)
Chemotherapeutic strategies have used a variety of drugs and hormonal agents that interfere with the basic machinery of the cell. (nature.com)

This process has led to the discovery of inhibitors with greater specificity, reduced side-effects and lower toxicity. (spandidos-publications.com)
First- and second-generation inhibitors classify FLT3 inhibitors according to FLT3 specificity: first-generation FLT3 inhibitors include sorafenib and midostaurin and second-generation inhibitors are represented by quizartinib, gilteritinib and crenolanib, among others. (dovepress.com)
These pumps have broad drug specificity and belong to a family of ATP-binding cassette (ABC) transporters, of which P-glycoprotein (PGP) is one of the most important members. (savedelicious.com)

This review summarizes the intracellular functions of Akt as a pivotal point of converging signaling pathways involved in cell growth, proliferation, apoptotis and neo‑angiogenesis, and focuses on the drug design strategies to develop potent anticancer agents targeting Akt. (spandidos-publications.com)
What pathways are this gene/protein implicaed in? (cancerindex.org)
Some are developing bispecific antibodies that can influence multiple and complementary immune pathways for greater therapeutic effect. (genengnews.com)
Cervical and ovarian carcinogenesis employ different pathways to achieve cellular immortalization, and this has a significant bearing on the evidence supporting the use of anti-angiogenic agents in the two malignancies. (cancernetwork.com)
The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone. (frontiersin.org)
In the present review, the role of Jak/STAT proteins and their regulators will be discussed in connection with osteoclastogenesis, since growing evidence indicates that a number of cytokines and growth factors utilizing Jak/STAT signaling pathways affect osteoclastogenesis. (koreascience.kr)

The BRAF V600E mutation may be a potential prognostic factor and therapeutic target for BC. (karger.com)
This review provides an overview of previous findings and ongoing research on LKB1, and substantiates the use of this kinase as a potential prognostic and predictive biomarker of breast cancer. (scirp.org)

3 , 4 Since 2020, older or unfit patients are treated by a non-intensive approach combining the hypomethylating agent azacitidine and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax given orally until progression. (dovepress.com)

Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. (biomedcentral.com)
Preliminary trials assessing combination therapy with anti-PD-1/PD-L1 plus anti-CTLA-4 immune-checkpoint inhibitors have documented considerable advantages in survival indices over single-agent immunotherapy. (biomedcentral.com)

Matrix assisted laser desorption ionization (MALDI) mass spectrometry is commonly used to analyze biological molecules such as proteins, peptides and lipids from cells or tissue. (koreascience.kr)

Protein kinase C (PKC) is a family of serine-threonine kinases that regulate many cellular processes including proliferation and survival. (endocrine-abstracts.org)
The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)

Therefore, Ku-DNA binding inhibitors seem to be a promising anticancer therapeutic strategy in combination with DNA DSB-inducing agents [11]. (termedia.pl)

The discovery process of Akt inhibitors has evolved from adenosine triphosphate (ATP)‑competitive agents to alternative approaches employing allosteric sites in order to overcome the high degree of structural similarity between Akt isoforms in the catalytic domain, and considerable structural analogy to the AGC kinase family. (spandidos-publications.com)
Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMAs) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). (haematologica.org)
The therapeutic potential of combinatorial approaches is highlighted by the recent FDA approval of nivolumab plus ipilimumab for patients with advanced melanoma. (biomedcentral.com)
Therapeutic approaches depend on disease subtype and patient's age, general status, and comorbidities. (dovepress.com)
Paralleling the emergence of targeted therapeutics in cancer treatment, a variety of experimental approaches has led to the conclusion that tumors bearing some specific genetic alterations may lead them to be uniquely sensitive to agents deregulating their cellular metabolism. (aacrjournals.org)

It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. (cancerindex.org)
The 5' cap open reading frame encodes a variety of non-structural proteins. (medsci.org)

In August 2014, the US Food and Drug Administration (FDA) approved bevacizumab for the treatment of advanced cervical cancer, the first gynecologic cancer for which an anti-angiogenic agent has demonstrated an advantage in overall survival (OS). (cancernetwork.com)
This represents a burden on public healthcare and a serious issue to be considered when designing the treatment plan of the patients, highlighting an urgent need to identify new predictive markers of therapeutic response, to ensure a better survival rate for the patients. (scirp.org)

A second generation of Akt has inhibitors emerged by incorporating a chemically reactive Michael acceptor template to target the nucleophile cysteines in the catalytic activation loop. (spandidos-publications.com)
Bellacosa A, Kumar CC, Di Cristofano A and Testa JR: Activation of AKT kinases in cancer: Implications for therapeutic targeting. (spandidos-publications.com)
They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
Preferential activation of microsomal diacylglycerol/protein kinase C signaling during glucose treatment (De Novo phospholipid synthesis) of rat adipocytes. (jci.org)
Cas9 nuclease can be converted into an RNA-guided DNA binding protein (dCas9) via inactivation of its two catalytic domains 12 , 13 and then fused to transcription activation domains. (cdc.gov)

Growth factors such as fibroblast growth factor (FGF), vascular endothelial cell growth factor (VEGF), and angiopoietin-1 (Ang1) are upregulated to stimulate angiogenesis, while downregulation of endogenous protein inhibitors (thrombospondin 1 and interferon) disrupts the balance of physiologic angiogenesis. (cancernetwork.com)

Here, we have determined the growth-inhibitory and proapototic mechanisms of 2 small molecule inhibitors of FLT3, AG1295 or PKC412, in hematopoietic progenitor cells, human leukemic cell lines, and primary AML cells expressing FLT3-ITD. (ashpublications.org)
Development of RTK inhibitors selective for FLT3 has emerged as attractive drugs for treatment of AML patients. (ashpublications.org)
Several inhibitors have been described, such as AG1295, CEP701, PKC412, and SU-11 248, with cytotoxic effects to cell lines and primary AML cells in vitro expressing mutant FLT3. (ashpublications.org)
FMS-like tyrosine kinase 3 ( FLT3 ) is one of the most frequently mutated genes in acute myeloid leukemia (AML). (dovepress.com)
Approximately 30% of the adult cases harbor an internal tandem duplication ( FLT3 -ITD) and 5- 10% a tyrosine kinase domain (TKD) amino acid substitution ( FLT3-TKD ). (dovepress.com)
The FLT3 inhibitors sorafenib, midostaurin, quizartinib and gilteritinib have been tested in monotherapy in several settings including refractory or relapsed AML (R/R AML), post-transplant maintenance as well as in combination with intensive chemotherapy (ICT) or non-intensity regimens. (dovepress.com)
Gilteritinib in combination with hypomethylating agent as well as quizartinib are not supported by solid randomized trial results for their use in FLT3-mutated AML patients. (dovepress.com)
Among the most mutated driver genes in AML is FMS-like tyrosine kinase 3 ( FLT3 ). (dovepress.com)

This gene is a member of the protein-tyrosine kinase oncogene family. (cancerindex.org)
What does this gene/protein do? (cancerindex.org)
CD177 antigen is a protein that in humans is encoded by the CD177 gene. (cd177signaling.com)
The FGFR3 gene produces various forms of the FGFR3 protein. (azd5582inhibitor.com)
Programmable DNA binding proteins have emerged as an exciting platform for engineering synthetic transcription factors for modulating endogenous gene expression 5 - 11 . (cdc.gov)

Less safe are cocaine (a stimulant and local anaesthetic) and ethanol (colloquially, the "alcohol" in alcoholic beverages, a widely available sedative consumed worldwide): the therapeutic indices for these substances are 15:1 and 10:1, respectively. (wikipedia.org)
2000. TLVs and BEIs: Threshold limit values for chemical substances and physical agents and biological exposure indices. (cdc.gov)

presented an overview of the intrinsic molecular subtypes of breast cancer, as well as their prognostic and therapeutic implications [16] summarized in the Table 1 . (scirp.org)

Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes. (bvsalud.org)

Ritonavir is a potent inhibitor of CYP3A4- and CYP2D6- mediated drug metabolism. (who.int)

0 or 40 g / kg iv granisetron in Bosutinib SRC inhibitor alternating cycles of chemotherapy until the end of the period. (cd177signaling.com)

Inhibitors of this kinase share some of the functional transcriptional suppression action elicited by corticosteroids. (reviewofophthalmology.com)

Arencibia JM, Pastor-Flores D, Bauer AF, Schulze JO and Biondi RM: AGC protein kinases: From structural mechanism of regulation to allosteric drug development for the treatment of human diseases. (spandidos-publications.com)
Some of these allosteric inhibitors alter the kinase conformation, while others directly compete with the protein substrates. (eurekaselect.com)
Another interesting family of allosteric inhibitors is represented by those compounds targeting the myristate-pocket of Bcr-Abl (myristate-pocket binders). (eurekaselect.com)

A higher therapeutic index is preferable to a lower one: a patient would have to take a much higher dose of such a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect. (wikipedia.org)

It has been reported that Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA DSB [11]. (termedia.pl)

To overcome this problem, Werewolf Therapeutics is utilizing Predator, a protein engineering technology, to create conditionally activated molecules called Indukines. (genengnews.com)

TDM is recommended for use in the treatment of psychiatric disorders with lithium due to its narrow therapeutic range. (wikipedia.org)
Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. (biomedcentral.com)
The Company's name was inspired by "The Day One Talk" that physicians have with patients and their families about an initial cancer diagnosis and treatment plan. (itbusinessnet.com)
Anti-angiogenic agents are an important adjuvant treatment strategy in gynecologic cancer. (cancernetwork.com)
Novo SM, Wedge SR, Stark LA. Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib . (ncl.ac.uk)
After an initial regression of the disease, a second course of therapy was given at a reduced dose due to the toxicity of the treatment, with an associated lesser therapeutic effect. (nature.com)

Anatomy16

Organisms8

Diseases1

Chemicals and Drugs162

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes47

Disciplines and Occupations2

Information Science3

Cyclin-depend4

Receptor14

EGFR7

Tumor15

Antineoplastic agents2

Targets8

Tyrosine kinase re1

Therapies10

Catalytic subunit2

Mutations7

Phosphatidylinositol 3-kina1

Novel therapeutic1

Resistance11

Selective inhibitor1

Gleevec3

Small molecule inhibitor2

Inhibition3

Pathway5

Apoptosis1

Clinical9

Subunit1

Immune checkpoint inhibitor1

Chemotherapeutic3

Specificity3

Pathways6

Potential prognostic2

BCL21

Checkpoint3

Peptides1

Serine2

Anticancer1

Approaches5

Encodes2

Survival2

Activation5

Angiogenesis1

FLT38

Gene5

Indices2

Molecular1

Downstream1

Potent1

Chemotherapy1

Transcriptional1

Allosteric3

Elicit1

Modulate1

Molecules1

Treatment6