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  • Tumor Cells
  • IG-105 showed a potent activity against human leukemia and solid tumors in breast, liver, prostate, lung, skin, colon, and pancreas with IC 50 values between 0.012 and 0.298 μmol/L. It was also active in drug-resistant tumor cells and not a P-glycoprotein substrate. (aacrjournals.org)
  • After a series of design, synthesis, and biological testing, we have identified a new tubulin ligand of N -(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide (IG-105), which showed a potent anticancer activity in a variety of human tumor cells in vitro and in vivo . (aacrjournals.org)
  • Proteins
  • This technique has been applied to measuring the interactions of antigens and antibodies, enzymes and substrates, membranes and ligands, and fluorescent cofactors and proteins. (google.com.au)
  • This study is an excellent example of the use of QSAR and structure-based design to aid the identification of putative ligand binding sites on proteins. (omicsonline.org)
  • 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)
  • 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)
  • 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)
  • efficacy
  • However, the more extensive use of chemotherapeutic drugs such as paclitaxel is often limited by its severe side effects, including hypersensitivity reactions, myelosuppression, and neurotoxicity, which may be attributed to their nonspecific systemic organ distribution and inadequate intratumor concentrations, resulting in suboptimal efficacy ( 2, 3 ). (aacrjournals.org)
  • Combination of IG-105 with known anticancer drugs largely improved the therapeutic efficacy. (aacrjournals.org)
  • Hits from these screens are then tested in cells and then in animals for efficacy. (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)
  • soluble
  • Polymeric micelles represent one of the most promising nanocarriers due to their unique core-shell structure formed by amphiphilic block copolymers, which could facilitate the solublization of poorly soluble drugs and protect the drugs from degradation and metabolism. (aacrjournals.org)
  • hormonal
  • 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)
  • metabolism
  • however, stand-alone chemotherapy drugs suffer from numerous problems including rapid in vivo metabolism and/or excretion, inability to access and penetrate cancer cells, and nonspecific uptake by healthy cells and tissue. (hindawi.com)
  • molecular
  • In the intensifying efforts to discover new, hopefully more therapeutically efficacious HDAC inhibitors, molecular modeling-based rational drug design has played an important role in identifying potential inhibitors that vary in molecular structures and properties. (mdpi.com)
  • Our work focuses on the discovery of small molecular weight tubulin ligands. (aacrjournals.org)
  • bound
  • Some newer types are called "mix-and-measure" assays because they do not require separation of bound ligands. (wikipedia.org)
  • In this technique, drug particles are enveloped in a plasma membrane-bound vesicle. (wikipedia.org)
  • Platinum nanoparticle seeds were prepared by the decomposition of Pt2(dba)3 in tetrahydrofuran (THF) under carbon monoxide (CO). These conditions produced Pt nanoparticles with weakly bound THF and CO ligands and an approximate diameter on 1.2 nm. (wikipedia.org)
  • receptor
  • High resolution screening of plant natural product extracts for estrogen receptor alpha and beta binding activity using an online HPLC-MS biochemical detection system. (springer.com)
  • A detection method is used to determine the presence and extent of the ligand-receptor complexes formed, and this is usually determined electrochemically or through a fluorescence detection method. (wikipedia.org)
  • Radioligands are used to measure the ligand binding to receptors and should ideally have high affinity, low non-specific binding, high specific activity to detect low receptor densities, and receptor specificity. (wikipedia.org)
  • 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)
  • Aside from its cofactor role for intracellular enzymes, FA also displays high affinity for the folate receptor (FR), a glycosylphosphatidyinositol-linked protein that captures its ligands from the extracellular milieu and transports them inside the cell via a non-destructive, recycling endosomal pathway. (wikipedia.org)
  • When this ligand, known to bind the FR, is added in excess of the folate conjugate, it outcompetes the conjugate, indicating that the folate conjugate specifically binds the FR, and not other receptors, in the process of receptor-mediated endocytosis. (wikipedia.org)
  • nanoparticles
  • Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. (aacrjournals.org)
  • The representative PEG 5k -CA 8 micellar nanoparticles possess the ideal properties for drug delivery, including high drug loading capacity, optimal particle size (20-60 nm), outstanding stability (more than 6 months at 4ºC), and sustainable drug release profile. (aacrjournals.org)
  • reported the influence of ligand and solvent effects on the size and shape of platinum nanoparticles. (wikipedia.org)
  • Hexadecylamine (HDA) was added to the purified reaction mixture and allowed to displace the THF and CO ligands over the course of approximately seven days, producing monodispersed spherical crystalline Pt nanoparticles with an average diameter of 2.1 nm. (wikipedia.org)
  • When the same procedure was followed using a stronger capping agent such as triphenyl phosphine or octanethiol, the nanoparticles remained spherical, suggesting that the HDA ligand affects particle shape. (wikipedia.org)
  • Research showed that alkylamine can coordinate with Pt2+ ion and form tetrakis(amine)platinate precursor and replace the original acac− ligand in Pt(acac)2, and oleic acid can further exchange with acac− and tune the formation kinetics of platinum nanoparticles. (wikipedia.org)
  • cytotoxic drug
  • The mode of cytotoxic drug action was determined by annexin binding, DNA fragmentation, and caspase activation. (uliege.be)
  • Often, a large percentage of cytotoxic drug administered to the patient does not reach the tumor environment but rather is distributed throughout the body, resulting in the many toxic effects associated with chemotherapy and a narrowing of the drug's therapeutic window. (hindawi.com)
  • hydrophobic drugs
  • To address this problem, a novel triblock copolymer has been developed to encapsulate several different hydrophobic drugs into stable polymer micelles. (hindawi.com)
  • We have recently developed a series of novel linear dendritic block copolymers (telodendrimers) comprising polyethylene glycol (PEG) and dendritic cholic acids (CA), which can encapsulate high concentrations of hydrophobic drugs such as paclitaxel and self-assemble to form stable core-shell micelles under aqueous condition ( 6-12 ). (aacrjournals.org)
  • Thus
  • 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)
  • 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)
  • Taxol
  • Agents acting at the process, such as Vinca alkaloids and Taxol analogues, have been used as first-line drugs for cancer patients. (aacrjournals.org)
  • The representative drugs in clinic of such mode of action are Vinca alkaloids (such as vincristine) that inhibit microtubule assembly and Taxol analogues (such as paclitaxel) that disrupt the microtubules disassembly ( 10 - 12 ). (aacrjournals.org)
  • chemotherapeutic agents
  • 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)
  • 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)
  • Synthesis
  • Burke JF, Duff PM, Pearson CK (1979) Effect of drugs on deoxyribonucleic acid synthesis in isolated mammalian cell nuclei. (springer.com)
  • inhibitors
  • 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)
  • 20 crystal structures with and without ligands have been published and in 2010 nearly a dozen small molecule c-Met inhibitors have been tested clinically. (wikipedia.org)
  • mechanistic
  • 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)
  • biological
  • An ideal delivery system should be composed of biocompatible and biodegradable materials, reproducibly assemble into the desired size range, encapsulate a wide range of drugs and drug classes, maintain particle size in biological media, have the ability to attach cell-specific targeting groups, and release the therapeutic at the site of disease. (hindawi.com)
  • 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)
  • competitive
  • 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)
  • Activator
  • Objective: Signal transducer and activator of transcription 3 (STAT3) is as a potential drug target for cancer and inflammation. (omicsonline.org)
  • chemotherapy
  • 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)
  • 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)
  • 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)
  • 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)
  • Intensification chemotherapy is identical to consolidation chemotherapy but a different drug than the induction chemotherapy is used. (wikipedia.org)
  • Combination chemotherapy involves treating a patient with a number of different drugs simultaneously. (wikipedia.org)
  • activity
  • The effects of valproic acid (VPA), an antiepileptic drug with histone deacetylase inhibitory activity, on mononuclear cells isolated from 40 CLL patients were evaluated. (uliege.be)
  • Nuclease activity via self-activation and anticancer activity of mononuclear copper (II) complex: Role of tertiary butyl group in the ligand frame, Manuscript under revision in Inorganic Chemistry 2012 , 51, 3343-45. (uta.edu)
  • There are two common strategies that are adopted for this type of experiment: Increasing the amount of radioligand added while maintaining both the constant specific activity and constant concentration of radioligand, or decreasing the specific activity of the radioligand due to the addition of an unlabeled ligand. (wikipedia.org)
  • Ligand specific recruitment of coregulators might be crucial for the agonist or antagonist activity of AR ligands. (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)
  • 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)
  • mechanism
  • Inactivation of the apoptotic pathway is an important mechanism that leads to tumor progression and tolerance to antitumor drugs ( 8 ). (aacrjournals.org)
  • We have illustrated the molecule mode of action of this compound and the mechanism of why IG-105 is active against drug-resistant cancer cells. (aacrjournals.org)
  • 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)
  • The drugs differ in their mechanism and side-effects. (wikipedia.org)
  • therapeutics
  • The EPR effect is a consequence of the disorganized nature of the tumor vasculature, which results in increased permeability of polymer therapeutics and drug retention at the tumor site. (hindawi.com)
  • clinical
  • 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)
  • The discovery of vitamin-mediated drug targeting in plants led to the hypothesis that folate-targeted therapies could be of clinical use. (wikipedia.org)
  • involves
  • 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)
  • approaches
  • Additional translational approaches, such as targeting telomeres using G-quadruplex ligands, should result in antitelomere agents, such as RHPS4, entering the clinic in the near future. (aacrjournals.org)
  • Specifically
  • 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)
  • cell
  • Afterwards, the empty FR returns to the cell surface where it can participate in another round of ligand-mediated endocytosis. (wikipedia.org)
  • binds
  • When this ligand, known to bind the FR, is added in excess of the folate conjugate, it outcompetes the conjugate, indicating that the folate conjugate specifically binds the FR, and not other receptors, in the process of receptor-mediated endocytosis. (wikipedia.org)
  • bone
  • 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)
  • induce
  • Mechanistically, immune cell depletion studies demonstrated that while CD8+ T cells are critical for antitumor immunity, CD4+ T cells are also required to induce a sustained long-lasting helper effect. (jove.com)
  • bind
  • Androgens, either agonists or antagonists, position themselves in the ligand-binding pocket (LBP) of the cytosolic AR and bind to the LBD, see figure 2. (wikipedia.org)
  • specific
  • There are two common strategies that are adopted for this type of experiment: Increasing the amount of radioligand added while maintaining both the constant specific activity and constant concentration of radioligand, or decreasing the specific activity of the radioligand due to the addition of an unlabeled ligand. (wikipedia.org)
  • Ligand specific recruitment of coregulators might be crucial for the agonist or antagonist activity of AR ligands. (wikipedia.org)
  • 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)
  • Patent
  • The "final product" of drug discovery is a patent on the potential drug. (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)
  • agent
  • Our results demonstrate that Pinus koraiensis pinecone is a readily available source of polyphenols, and the purified PPP could be a promising natural antitumor agent for applications in functional foods. (mdpi.com)
  • The (-)-enantiomer is a cell cycle inhibitor, which can be potentially used as an antitumor agent. (aspetjournals.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)
  • When the same procedure was followed using a stronger capping agent such as triphenyl phosphine or octanethiol, the nanoparticles remained spherical, suggesting that the HDA ligand affects particle shape. (wikipedia.org)
  • cells
  • Herein is reported a novel antibody-dependent-cytotoxicity-FACS-assay based on a three-dimensional spheroid or an aggregate formed of lymphoma cells and natural killer cells. (patentsencyclopedia.com)
  • The basal promoter activity of Lenti-CMV-TK and Lenti-STAT3-NF-κB-TK in MDA-MB-231 cells was compared by 3 H-FEAU uptake assay. (thno.org)
  • In clonogenic assay, cells expressing Lenti-CMV-TK were 2-fold more sensitive to GCV than Lenti-STAT3-NF-κB-TK transduced cells. (thno.org)
  • This platform may also be an alternative strategy to handle with drug-resistant cancer cells. (thno.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)
  • Hits from these screens are then tested in cells and then in animals for efficacy. (wikipedia.org)
  • known
  • Later, small molecules were synthesized to specifically target a known physiological/pathological pathway, avoiding the mass screening of banks of stored compounds. (wikipedia.org)
  • Identification
  • 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)
  • 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)
  • development
  • 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)
  • discovery
  • 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)
  • Drug discovery is done by pharmaceutical companies, with research assistance from universities. (wikipedia.org)
  • The discovery of vitamin-mediated drug targeting in plants led to the hypothesis that folate-targeted therapies could be of clinical use. (wikipedia.org)
  • therapy
  • Moreover, developing a new drug for cancer therapy is labor intensive and sometimes cost prohibitive. (readbyqxmd.com)
  • 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)
  • small
  • As of 2010[update] antiandrogens are small molecules and can be either steroidal or nonsteroidal depending on ligand chemistry. (wikipedia.org)
  • line
  • Next, the antiproliferative effects of PPP on seven cancer cell lines, including A375 (human skin melanoma cancer cell line), A549 (human lung cancer cell line), SH-SY5Y (human neuroblastoma cell line), LOVO (human colon cancer stem cell line), MCF-7 (human breast cancer cell line), HeLa (human cervical cancer line), and HT29 (human colon cancer line), were examined by MTT assays. (mdpi.com)
  • main
  • The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). (readbyqxmd.com)
  • effect
  • 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)
  • research
  • Research showed that alkylamine can coordinate with Pt2+ ion and form tetrakis(amine)platinate precursor and replace the original acac− ligand in Pt(acac)2, and oleic acid can further exchange with acac− and tune the formation kinetics of platinum nanoparticles. (wikipedia.org)