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  • 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)
  • Cells
  • A high-throughput screen with isogenic PTEN+/+ and PTEN-/- cells identifies CID1340132 as a novel compound that induces apoptosis in PTEN and PIK3CA mutant human cancer cells. (biomedsearch.com)
  • Because inactivation of PTEN is a somatic event, PTEN mutations represent an important genetic difference between cancer cells and normal cells and therefore a potential anticancer drug target. (biomedsearch.com)
  • In an effort to identify small molecules that preferentially kill cells with mutations of PTEN, the authors developed and implemented a high-throughput, paired cell-based screen composed of parental HCT116 cells and their PTEN gene-targeted derivatives. (biomedsearch.com)
  • From 138 758 compounds tested, two hits were identified, and one, N'-[(1-benzyl-1H-indol-3-yl)methylene]benzenesulfonohydrazide (CID1340132), was further studied using a variety of cell-based models, including HCT116, MCF10A, and HEC1A cells with targeted deletion of either their PTEN or PIK3CA genes. (biomedsearch.com)
  • To date, the majority of the antiangiogenesis drug studies have been performed using endothelial cells isolated from either capillaries or large vessels. (ahajournals.org)
  • Cancer cell line tubulins are useful for developing drugs targeted toward cancer cells. (cytoskeleton.com)
  • Brief heating of these drugs-treated cells at 65° for 10 min resulted in a rapid reduction in the number of protein/DNA complexes. (aspetjournals.org)
  • H-460 cells undergo apoptosis, which increases with longer exposure to the compound and also after exposure to P276-00 for 48 h followed by recovery. (aacrjournals.org)
  • Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. (aacrjournals.org)
  • However, there has been a renewed interest in drug screening focused on compound-induced phenotypic changes in live cells ( 3, 4 ). (aacrjournals.org)
  • It is imperative to uncover new therapeutic drug on targeting cancer stem cells [ 6 ]. (hindawi.com)
  • Lipophilicity makes compounds more stable because of improved lactone partitioning into red blood cells and consequently less hydrolysis of the lactone. (wikipedia.org)
  • Hits from these screens are then tested in cells and then in animals for efficacy. (wikipedia.org)
  • Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow, digestive tract and hair follicles. (wikipedia.org)
  • Because of the effect on immune cells (especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the immune system against self (so-called autoimmunity). (wikipedia.org)
  • 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)
  • 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)
  • clinical
  • 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)
  • A number of studies have shown that the clinical efficacies of these drugs correlate with their abilities to induce topoisomerase-mediated DNA cleavage ( 12-14 ). (aspetjournals.org)
  • We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. (aacrjournals.org)
  • 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)
  • The availability of compound libraries containing drugs with documented clinical use makes unbiased screening for repositioning candidates an attractive approach. (aacrjournals.org)
  • 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)
  • 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)
  • Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials. (wikipedia.org)
  • The drug requires very expensive Phase I, II and III clinical trials, and most of them fail. (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)
  • 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)
  • 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)
  • 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)
  • Burke JF, Duff PM, Pearson CK (1979) Effect of drugs on deoxyribonucleic acid synthesis in isolated mammalian cell nuclei. (springer.com)
  • 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
  • Drugs activating BK channels therefore bear substantial therapeutic potential, but their deployment has been hindered in part because the mode of action remains obscure. (uef.fi)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. (hindawi.com)
  • In this study, we first successfully screened for an active component, named YMGKI-1, from natural products of Antrodia cinnamomea Mycelia (ACM), which can target the stemness properties of HNSCC. (hindawi.com)
  • 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)
  • cancer
  • Drug discovery remains to be the main focus for biomedical research and represents the essence of antiangiogenesis cancer research. (ahajournals.org)
  • 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)
  • 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)
  • These findings provide a new drug candidate from purified components of ACM as an alternative therapy for head and neck cancer in the future. (hindawi.com)
  • 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)
  • 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)
  • development
  • 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)
  • 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)
  • 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)
  • 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)
  • important
  • 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)
  • 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)
  • substantial
  • These platforms such as organ-on-a-chip, biological scaffolding, or microdrop techniques offer substantial advantages in evaluating disease mechanisms, drug discovery, and toxicity testing and potentially, for tissue-replacement therapies. (genengnews.com)
  • proteins
  • The foundations for which ligand binding assay have been built are a result of Karl Landsteiner, in 1945, and his work on immunization of animals through the production of antibodies for certain proteins. (wikipedia.org)
  • suggests
  • This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system. (nih.gov)
  • studies
  • However, the aim of these studies was to elucidate further the mode of binding of these compounds to DNA, and all of these studies involved the direct measurement of the fluorescent test compound itself. (google.com.au)