• Tumor
  • However, it remains a substantial challenge to identify compounds that target loss-of-function events such as mutations of tumor suppressors. (biomedsearch.com)
  • Taken together, these data validate a cell-based screening approach for identifying lead compounds that target cells with specific tumor suppressor gene mutations and describe a novel compound with preferential killing activity toward PTEN and PIK3CA mutant cells. (biomedsearch.com)
  • Targeting of molecular pathways involved in such tumor angiogenetic processes by using specific drugs or inhibitors is important for developing new anticancer therapies. (ahajournals.org)
  • We will also highlight the potential of zebrafish for identifying antitumor angiogenesis drugs to block tumor development and progression. (ahajournals.org)
  • 11 , 12 To design drugs that can be used to block such malignant processes, recent advanced strategies were aimed to better understand tumor vessels formation and normalization. (ahajournals.org)
  • 4. Cancer tubulin (cell line and tumor derived) polymerization assays to determine IC50 of anti-tumor drugs, 4 to 22 compounds, results turnaround within 3 weeks. (cytoskeleton.com)
  • Studies to show tumor sensitivity using clonogenic assay in 22 human xenografts indicated that P276-00 was ∼26-fold more potent than cisplatin, and further, it was also found to be active against cisplatin-resistant tumors of central nervous system, melanoma, prostate, and renal cancers. (aacrjournals.org)
  • Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). (nih.gov)
  • Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. (aacrjournals.org)
  • Both telomerase inhibitors and telomere interactive molecules have shown stand-alone antitumor activity at nontoxic doses against a variety of human tumor xenografts in mice. (aacrjournals.org)
  • OcellO, a Netherlands-based contract research organization that offers drug screening and profiling services using 3D cell culture models of disease, says it has expanded the utility of patient-derived (PDX) mouse models by offering in vitro assays using 3D culture of the same tumor materials. (genengnews.com)
  • Despite technical obstacles, Dr. Price cited advantages of the company's high-throughput in vitro PDX screening platform: the supply of PDX tumor is essentially unlimited in amount, and the same tumor can be sourced repeatedly "[This is] unlike patient tumor, which is limited in amount and can only be obtained once," he points out. (genengnews.com)
  • Dr. Price also noted that a major headache in drug discovery is the translation between in vitro and in vivo studies-results of in vitro studies with cell lines can often not be recapitulated in vivo , partly because the biology of a 2D monolayer and a solid tumor are different and because the cell lines used in vitro differ from the tumors in mice. (genengnews.com)
  • Cytotoxicity is used when compounds or extracts show in vitro (in cells) activity against tumor cell lines. (schoolbag.info)
  • inhibit
  • We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. (nih.gov)
  • Herein, we show that all five compounds inhibit mitochondrial respiration. (aacrjournals.org)
  • mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). (wikipedia.org)
  • Drugs that inhibit hepatic glucuronidation, such as indomethacin, nordazepam, acetylsalicylic acid (aspirin) and trimethoprim decreased the elimination rate and increased the therapeutic strength of the medication. (wikipedia.org)
  • biologic
  • Therefore, in order to be sure what process or processes are producing the measured heat flow, great care must be taken in both experimental design and in the initial use of related chemical, physical and biologic assays. (wikipedia.org)
  • isolation
  • The recent development of new bioassay methods has facilitated progress in the BDFI (bioactivity-directed fractionation and isolation) of many useful bioactive compounds from natural sources (1). (schoolbag.info)
  • utilize
  • Specifically, despite the human body's endogenous receptors, hormones, and other neurotransmitters, pharmacologists utilize assays in order to create drugs that are selective, or mimic, the endogenously found cellular components. (wikipedia.org)
  • Streptomyces have the ability to utilize many different compounds as part of their metabolism including sugars, amino acids, and alcohols through the production of extracellular enzymes. (wikipedia.org)
  • activity
  • Using this approach, approved, discontinued, or withdrawn drugs with unrecognized anticancer activity can be rapidly advanced into clinical trials, because much of the required documentation already exists. (aacrjournals.org)
  • A large percentage of compounds that bind to DNA are known to have mutagenic and/or carcinogenic activity and hence, it is of interest to have a rapid reproducible method for screening compounds that interact with DNA. (google.com.au)
  • Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. (stanford.edu)
  • Reduced drug-HSA interactions could result in improved activity. (wikipedia.org)
  • BNP1350 which belongs to the series of karenitecins exhibits cytotoxic activity and ability to overcome drug resistance. (wikipedia.org)
  • therapeutic
  • To design new therapeutic strategies and to test the efficacy of antiangiogenic cancer drugs, researchers and clinicians need models in which these malignant angiogenic events can be replicated and then studied at genetic, biochemical, molecular, and cellular levels. (ahajournals.org)
  • Both upper- and middle-class medicines are used as therapeutic drugs, but the former medicines are not as toxic as the latter. (schoolbag.info)
  • Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery. (wikipedia.org)
  • derivatives
  • These drugs, referred to as topoisomerase poisons, include synthetic intercalators (e.g., mAMSA, mitoxantrone), antibiotics from microbes (e.g., anthracyclines, actinomycin D), and derivatives of plant metabolites [e.g., camptothecin derivatives such as CPT-11 and topotecan and epipodophyllotoxin derivatives such as VP-16 (etoposide) and VM-26 (teniposide)] ( 4-10 ). (aspetjournals.org)
  • As a result of this screening, we found that antitumor indolocarbazole derivatives and blue pigment bulgarein induced topoisomerase I-mediated DNA cleavage ( 15 , 16 ) and that flavonoids (e.g., genistein and orobol), plant naphthoquinones (e.g., plumbagin and shikonin), and antitumor antibiotics (e.g., streptonigrin and members of the terpentecin family) induced topoisomerase II-mediated DNA cleavage ( 17-20 ). (aspetjournals.org)
  • interactions
  • Silatecans or 7-silylcampthothecins have shown reduced drug-HSA interactions which contributes to its blood stability and they can also cross the blood brain barrier. (wikipedia.org)
  • Ligand binding assays provide a measure of the interactions that occur between two molecules, such as protein-bindings, as well as the degree of affinity (weak, strong, or no connection) for which the reactants bind together. (wikipedia.org)
  • Examples
  • Examples of drug compounds isolated from crude preparations are morphine, the active agent in opium, and digoxin, a heart stimulant originating from Digitalis lanata. (wikipedia.org)
  • Some common examples of platinum precursors include potassium hexachloroplatinate (K2PtCl6) or platinous chloride (PtCl2) Different combinations of precursors, such as ruthenium chloride (RuCl3) and chloroplatinic acid (H2PtCl6), have been used to synthesize mixed-metal nanoparticles Some common examples of reducing agents include hydrogen gas (H2), sodium borohydride (NaBH4) and ethylene glycol (C2H6O2), although other alcohols and plant-derived compounds have also been used. (wikipedia.org)
  • concentration
  • Essential aspects of binding assays include, but are not limited to, the concentration level of reactants or products (see radioactive section), maintaining the equilibrium constant of reactants throughout the assay, and the reliability and validity of linked reactions. (wikipedia.org)
  • detection
  • Applications discussed range from measurement of slow oxidative degradation of polymers and instability of hazardous industrial chemicals to detection of bacteria in urine and evaluation of the effects of drugs on parasitic worms. (wikipedia.org)
  • molecules
  • We used a concept of drug repositioning-using known molecules for new indications. (aacrjournals.org)
  • Later, small molecules were synthesized to specifically target a known physiological/pathological pathway, avoiding the mass screening of banks of stored compounds. (wikipedia.org)
  • Ligand binding assays (LBA) is an assay, or an analytic procedure, whose procedure or method relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. (wikipedia.org)
  • potential
  • These prototype trials will be extremely informative in determining the role of the telomerase/telomere pathway in clinical oncology and, moreover, whether drugs targeting the unlimited replicative potential of cancer will find a place in cancer chemotherapy. (aacrjournals.org)
  • Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinity, selectivity (to reduce the potential of side effects), efficacy/potency, metabolic stability (to increase the half-life), and oral bioavailability. (wikipedia.org)
  • The "final product" of drug discovery is a patent on the potential drug. (wikipedia.org)
  • wherein
  • Stereochemistry at C3 was determined by Marfey's analysis, wherein the compound was ozonized and subsequently hydrolyzed to obtain cysteic acid from the thiazoline ring and attached terminal alkene. (wikipedia.org)
  • nitrogen
  • Majority of these compounds are nitrogen containing and belong to non-ribosomal peptide (NRPs) or mixed polyketide-NRP natural products. (frontiersin.org)
  • The chemical shifts of ring carbons adjacent to the sulfur and nitrogen heteroatoms were compared to 13C NMR data from model compounds. (wikipedia.org)
  • Basic nitrogen in a carbon chain at position 7 makes the compound more hydrophilic and hence more water-soluble. (wikipedia.org)
  • advancement
  • As a direct result of these monumental findings, researchers have continued the advancement of ligand binding assays in many facets in the fields of biology, chemistry, and the like. (wikipedia.org)
  • fluorescence
  • This is also a direct assay and is not dependent on the use of fluorescence polarization (Kapuscinski, J. and Skoczyles, B., Analytical Biochem. (google.com.au)
  • reactions
  • citation needed] A number of these side effects are associated with the excipient used, Cremophor EL, a polyoxyethylated castor oil, and allergies to cyclosporine, teniposide, and other drugs containing polyoxyethylated castor oil may indicate increased risk of adverse reactions to paclitaxel. (wikipedia.org)
  • development
  • Cytoskeleton, Inc. has been a reliable source of compound screening services in the areas of pre-clinical drug development programs and early compound screening in primary HTS projects, as well as secondary screening and compound target validation. (cytoskeleton.com)
  • Cytoskeleton, Inc. has been a reliable source of compound screening data, custom protein production, assay design & development and antibody/ELISA development for past two decades. (cytoskeleton.com)
  • The cancer drug development process has become increasingly costly and inefficient resulting in few new highly effective drugs reaching the market yearly ( 1 ). (aacrjournals.org)
  • The relatively recent clinical success of bortezomib, particularly in multiple myeloma, has established the validity of the proteasome as a viable target for anticancer drug development. (aacrjournals.org)
  • Such advances provide researchers with the ability not only to quantify hormones and hormone receptors, but also to contribute important pharmacological information in drug development and treatment plans. (wikipedia.org)
  • Through the development of RIA technology, researchers have been able to move beyond the use of radioactivity, and instead, use liquid- and solid-phase, competitive, and immunoradiometric assays. (wikipedia.org)
  • mammalian
  • New saintopin-type antibiotics (e.g., saintopin, saintopin E, UCE1022, UCE6) with a naphthacene-dione structure have been discovered through our mechanistically oriented screening using purified mammalian DNA topoisomerases. (aspetjournals.org)
  • important
  • Arguably, the availability of the types of drugs discussed in this article (able to target protein breakdown/turnover) could have aided their cause by adding translational relevance to important biochemical pathways described by Rose and colleagues. (aacrjournals.org)
  • Numerous important bioactive compounds have been, and continue to be, isolated worldwide from natural sources. (schoolbag.info)
  • He discovered two important drugs: etoposide and ciclosporin. (wikipedia.org)
  • Filamentous soil bacteria from the genus Streptomyces are important sources of biologically active compounds used in pharmaceutical and agrochemical industries. (wikipedia.org)
  • cancer
  • Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. (ahajournals.org)
  • Several of these peptides are currently under trial for developing new drugs against various disease areas, including inflammatory, cancer, neurodegenerative disorders, and infectious disease. (frontiersin.org)
  • An effective cancer blood biomarker screening strategy must distinguish aggressive from non-aggressive tumors at an early, intervenable time. (stanford.edu)
  • Our model and screening strategy offer broad impact in their applicability to any solid cancer and the biomarkers they shed, thereby allowing a distinction between aggressive vs. non-aggressive tumors using blood biomarker sampling data alone. (stanford.edu)
  • This highly cited 1999 Cancer Research article from Adams and colleagues was published during the period when this drug was transitioning from preclinical studies to phase I clinical trial status. (aacrjournals.org)
  • In 1989 the United States Food and Drug Administration (FDA) approved it for use the treatment of prostate cancer. (wikipedia.org)
  • Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a category of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. (wikipedia.org)
  • Importantly, the use of drugs (whether chemotherapy, hormonal therapy or targeted therapy) constitutes systemic therapy for cancer in that they are introduced into the blood stream and are therefore in principle able to address cancer at any anatomic location in the body. (wikipedia.org)
  • Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. (wikipedia.org)
  • Combined modality chemotherapy is the use of drugs with other cancer treatments, such as surgery, radiation therapy, or hyperthermia therapy. (wikipedia.org)
  • This was approved by the U.S. Food and Drug Administration in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. (wikipedia.org)
  • Crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA). (wikipedia.org)
  • secondary
  • These compounds include both primary and secondary metabolites isolated mainly from plants, as well as from the animal and mineral kingdoms. (schoolbag.info)
  • target
  • To address these challenges, we combined two major advances in technology: (i) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (ii) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. (nih.gov)
  • In the 1990s there was a dramatic change in this field due to studies on the mechanism of action of rapamycin and the identification of the drug target. (wikipedia.org)
  • cellular
  • At Cambridge Healthtech Institute's 15th annual High-Content Analysis and 3D Screening meeting, held November 2017 in Boston, participants from academia and pharma companies will focus on advancements in HCA technologies and applications, including screening of 3D and physiologically relevant cellular models, data analysis techniques, and will present case studies and strategies for successful drug discovery. (genengnews.com)
  • candidates
  • This article summarizes research on many different useful compounds isolated or developed from plants with an emphasis on those discovered recently by the laboratories of the authors as antitumor and anti-HIV clinical trial candidates. (schoolbag.info)
  • exposure
  • These drugs interfere with the breakage-rejoining reaction of topoisomerases by stabilizing key reaction intermediates of topoisomerases ("cleavable complex"), which can be detected as DNA strand breaks on exposure to a strong protein denaturant such as SDS or alkaline ( 4-6 , 11 ). (aspetjournals.org)
  • AZT has been used for post-exposure prophylaxis (PEP) in combination with another antiretroviral drug called lamivudine. (wikipedia.org)
  • protein
  • many of them are multi-protein assays that might have protein complexes of 3 or more subunits, e.g., a soluble sarcomere format and the Arp2/3 complex based assay. (cytoskeleton.com)
  • fail
  • Although binding assays are simple, they fail to provide information on whether or not the compound being tested affects the target's function. (wikipedia.org)
  • high-throughput
  • OcellO's high content imaging and analysis platform, it says, enables in-depth evaluation of drug effects in a robust, high-throughput format. (genengnews.com)
  • effects
  • Paclitaxel drug eluting coated stents for femoropopliteal artery placement are sold under the trade name Zilver PTX by Cook Medical, Inc. Common side effects include nausea and vomiting, loss of appetite, change in taste, thinned or brittle hair, pain in the joints of the arms or legs lasting two to three days, changes in the color of the nails, and tingling in the hands or toes. (wikipedia.org)
  • large
  • Modern drug discovery is thus usually a capital-intensive process that involves large investments by pharmaceutical industry corporations as well as national governments (who provide grants and loan guarantees). (wikipedia.org)
  • Meanwhile, for disorders whose rarity means that no large commercial success or public health effect can be expected, the orphan drug funding process ensures that people who experience those disorders can have some hope of pharmacotherapeutic advances. (wikipedia.org)
  • Only a limited number of compounds are available for clinical use despite the fact that a very large variety of antiandrogen compounds have been discovered and researched. (wikipedia.org)
  • crude
  • In TCM, crude herbal drugs formerly were divided into three categories: upper-, middle-, and lower-class medicines. (schoolbag.info)