• pharmacology
  • Ligand binding assays are used primarily in pharmacology for various demands. (wikipedia.org)
  • In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. (wikipedia.org)
  • Later chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that have a desirable therapeutic effect in a process known as classical pharmacology. (wikipedia.org)
  • Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compounds libraries against isolated biological targets which are hypothesized to be disease modifying in a process known as reverse pharmacology. (wikipedia.org)
  • This made for the beginning of the modern era in pharmacology, as pure chemicals, instead of crude extracts of medicinal plants, became the standard drugs. (wikipedia.org)
  • This approach is known as classical pharmacology, forward pharmacology, or phenotypic drug discovery. (wikipedia.org)
  • inhibitors
  • Screening of small molecule inhibitors that suppress the Progression Elevated Gene-3-promoter may provide relevant lead compounds for cancer therapy that can be combined with further structure-based approaches leading to the development of novel compounds for cancer therapy. (nih.gov)
  • From a set of weakly potent lead compounds, using in silico screening and small library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been identified as inhibitors of the MDM2-p53 interaction. (ox.ac.uk)
  • 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)
  • The discovery of small chemical inhibitors of human Kinesin-5 through a pioneering in vitro phenotypic screening on cancer cell lines has led to both the development of new anticancer therapeutic agents, and to novel tools to probe the mechanism of microtubule motor proteins. (wikipedia.org)
  • 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)
  • 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)
  • RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. (clinicaltrials.gov)
  • The present study aimed to investigate the antitumor effects of virosecurinine by inducing the apoptosis of leukemic K562 cells and to examine the underlying mechanisms. (nih.gov)
  • The cell counting kit (CCK)‑8 method was used to detect the antitumor effect of K562 cells in vitro. (nih.gov)
  • In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. (wikipedia.org)
  • While some drugs and radioimaging agents are delivered to cells as folate conjugates in a one-to-one folate-to-conjugate ratio, folate-targeted liposomes allow for the delivery of larger amounts of chemotherapeutic agents. (wikipedia.org)
  • Tetramer assays are used for single-cell phenotyping and cell counting, and offer an important advantage over other methods, such as ELISPOT and single-cell PCR because they enable the recovery and further study of sorted cells. (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)
  • Interactions
  • Reduced drug-HSA interactions could result in improved activity. (wikipedia.org)
  • 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)
  • The idea that the effect of a drug in the human body is mediated by specific interactions of the drug molecule with biological macromolecules, (proteins or nucleic acids in most cases) led scientists to the conclusion that individual chemicals are required for the biological activity of the drug. (wikipedia.org)
  • Compounds
  • Inhibition of Abl kinase in biochemical assays was maintained for most compounds, but in general the kinase selectivity profile differed from that of 1 with nearly equipotent inhibition of the wild-type and the Imatinib resistant Abl T(315)I mutant. (uni-regensburg.de)
  • Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. (nih.gov)
  • Many natural compounds have led to the discovery of drugs used to treat human disease. (wikipedia.org)
  • In 1969, Stähelin made the key decision to include a test system for immunosuppression into the general screening program at Sandoz for compounds and extracts. (wikipedia.org)
  • One of the most potent compounds is the oxyiminomethyl derivative ST1481 that has the advantage to overcome drug resistance caused by transport systems. (wikipedia.org)
  • 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)
  • Later, small molecules were synthesized to specifically target a known physiological/pathological pathway, avoiding the mass screening of banks of stored compounds. (wikipedia.org)
  • 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)
  • anticancer
  • The dolastatin series of unique peptides, originally discovered as constituents of the sea hare Dolabella auricularia, is of increasing importance in providing biological leads, especially to new and useful anticancer drugs. (nih.gov)
  • It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. (wikipedia.org)
  • ligands
  • From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis. (wikipedia.org)
  • Some newer types are called "mix-and-measure" assays because they do not require separation of bound ligands. (wikipedia.org)
  • Apoptosis
  • We have investigated the effects of the organic arsenical, melarsoprol (a drug used for treatment of trypanosomiasis), upon induction of apoptosis in cell lines representative of chronic B-cell lymphoproliferative disorders. (biomedsearch.com)
  • effects
  • Results of these studies suggest that melarsoprol shows promising therapeutic activity in these diseases, and a study to evaluate clinical effects of this drug has been initiated. (biomedsearch.com)
  • Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. (wikipedia.org)
  • The ligand-binding assay methodology quantified the concentration of the hormone in the test material by comparing the effects of the test sample to the results of varying amounts of known protein (ligand). (wikipedia.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 drugs differ in their mechanism and side-effects. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Phase
  • PURPOSE: Phase II trial to determine the reliability of a test for measuring drug resistance to paclitaxel in patients with metastatic breast cancer. (clinicaltrials.gov)
  • 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)
  • The drug requires very expensive Phase I, II and III clinical trials, and most of them fail. (wikipedia.org)
  • clinical
  • Determine prospectively the predictive value of the EDR assay relative to clinical outcome by correlating assay results with clinical tumor response and time to tumor progression during paclitaxel therapy in these patients. (clinicaltrials.gov)
  • Patients' clinical response to paclitaxel therapy is compared with the response predicted by the EDR assay. (clinicaltrials.gov)
  • The discovery of vitamin-mediated drug targeting in plants led to the hypothesis that folate-targeted therapies could be of clinical use. (wikipedia.org)
  • 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)
  • metastatic
  • OBJECTIVES: I. Evaluate the proportion of patients with extreme, intermediate, and low drug resistance to paclitaxel using the Extreme Drug Resistance (EDR) Assay in patients with previously treated metastatic breast cancer. (clinicaltrials.gov)
  • In addition, an in vivo experimental metastasis model also showed that treatment with the drugs resulted in a significantly lower number of metastatic pulmonary nodules relative to control mice. (nih.gov)
  • 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)
  • reactions
  • 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)
  • resistance
  • Patients' tumor tissue samples are collected by excisional biopsy, core biopsy, or malignant fluid aspiration, then tested by the Extreme Drug Resistance (EDR) Assay to determine probability of drug resistance to paclitaxel. (clinicaltrials.gov)
  • paclitaxel
  • Assess response to paclitaxel therapy in patients who have undergone a pretreatment EDR assay. (clinicaltrials.gov)
  • Paclitaxel drug eluting coated stents for coronary artery placement are sold under the trade name Taxus by Boston Scientific in the United States. (wikipedia.org)
  • Paclitaxel is one of several cytoskeletal drugs that target tubulin. (wikipedia.org)
  • binds
  • Mytomycin C (MC), an antibiotic produced by S. lavendulae, exhibits cytotoxicity when the activated drug covalently binds complementary strands of DNA. (wikipedia.org)
  • The second locus (mrd) binds with MC as a complex which prevents drug activation. (wikipedia.org)
  • Yeast three-hybrid assays have shown that this protein binds to the stem loops within the 3'UTR of the POLB mRNA, however the exact mechanism in how this protein regulates gene expression is still to be determined. (wikipedia.org)
  • Human
  • Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis. (wikipedia.org)
  • 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)
  • effect
  • The effect of only 10 μM of each drug was assessed in CMT93 (panel C). (nih.gov)
  • 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)
  • inhibit
  • 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)
  • therapy
  • Targeted drug therapy is advantageous because it deposits the drug at the specific location where it can be most useful in treating the disease. (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)
  • Combined modality chemotherapy is the use of drugs with other cancer treatments, such as surgery, radiation therapy, or hyperthermia therapy. (wikipedia.org)
  • Evaluation
  • MHC tetramers are used in studies of pathogen immunity and vaccine development, in evaluation of antitumor responses, in allergy monitoring and desensitization studies, and in autoimmunity. (wikipedia.org)
  • involves
  • 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)
  • Discovering drugs that may be a commercial success, or a public health success, involves a complex interaction between investors, industry, academia, patent laws, regulatory exclusivity, marketing and the need to balance secrecy with communication. (wikipedia.org)
  • Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). (wikipedia.org)
  • Combination chemotherapy involves treating a patient with a number of different drugs simultaneously. (wikipedia.org)
  • treatments
  • Testing patients' blood or bone marrow to find out if their type of cancer may be sensitive to a specific drug may help doctors choose more effective treatments. (clinicaltrials.gov)
  • Flow
  • As a flow-cytometry-based application, tetramers are also easy to use and have a short assay time, similar to Antibody-based flow cytometry studies. (wikipedia.org)
  • 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)
  • treatment
  • 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)
  • In 1989 the United States Food and Drug Administration (FDA) approved it for use the treatment of prostate cancer. (wikipedia.org)
  • Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. (wikipedia.org)
  • biological
  • 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)