Modulateurs d'enzymes

<p>Inhibitor of IKKβ serine kinase</p>

<p>Epalrestat is a carboxylic acid derivative that is used for the treatment of diabetic neuropathy. This drug is an aldose reductase inhibitor and aims to reduce the accumulation of intracellular sorbitol. Studies in rats have shown this drug to improve morphological abnormalities of nerves.</p>

<p>Ubenimex is a protease inhibitor drug that is being studied for the treatment of acute myelocytic leukemia. This drug is an aminopeptidase N, B and leukotriene A4 hydrolase inhibitor. It is also used in the treatment of hypercholesterolaemia.</p>

<p>Inhibitor of Flk-1/KDR receptor tyrosine kinases, a vascular endothelial growth factor receptor (VEGF) receptor expressed on precursor and mature forms of endothelial cells. SU 5416 also inhibits other tyrosine kinases, including c-KIT and FLT-3. Has therapeutic potential as an anti-angiogenic agent for the treatment of cancer.</p>

<p>Decitabine is a synthetic cytosine analogue that incorporates into DNA and prevents DNA methylation via DNA (cytosine-5)-methyltransferase 1 (DNMT1) inhibition. It has demonstrated potent anti-leukaemic effects attributed to cell cycle arrest and induction of apoptosis. Also, it has anti-growth effects on solid tumor cell lines.<br>Decitabine is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>Mevastatin is a drug that inhibits the synthesis of cholesterol and has been used to treat hypercholesterolemia. It binds to the hydroxyl group at position 3 on the mevalonate molecule, which prevents the formation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) and consequently reduces the production of cholesterol. Mevastatin has been shown to inhibit mitochondrial functions in wild-type strain yeast cells and myeloma cell lines, which may be due to receptor activity.</p>

<p>Inhibitor of glycogen phosphorylase and alpha-glucosidases</p>

<p>Selective inhibitor of the interaction between the UNC119 chaperone and its cargo. Squarunkin A inhibits activation of Src kinase by interrupting the interaction between the myristoylated peptide at the N-terminus of the Src kinase and UNC119A chaperone (IC50 = 10 nM). Squarunkin A impairs the UNC119-mediated enrichment of plasma membrane with non-receptor protein tyrosine kinase Src, resulting in the decrease in Src autophosphorylation and decreased oncogenic Src signalling.</p>

<p>Parecoxib is a COX-2 inhibitor and belongs to the group of pharmacological agents. It is a prodrug of valdecoxib that is used for the treatment of osteoarthritis and rheumatoid arthritis, as well as other conditions where the reduction in pain and inflammation are desired.</p>

<p>Inhibits lysophosphatidylserine hydrolysis by the integral membrane serine hydrolase ABHD12 (IC50 = 1.3 µM). Raised levels of lysophosphatidylserine were observed in mouse brain in vivo and in primary human macrophages. DO 264 had proinflammatory effects, following infection with lymphocytic choriomeningitis virus (LCV) clone 13 in mice, resulting in severe inflammatory lung damage.</p>

<p>Inhibitor of ataxia telangiectasia mutated (ATM) kinase and AKT kinase with anti-cancer activity. ATM is a nuclear protein kinase and a signal transducer sensing DNA damage as well as controlling double strand DNA break (DSB) repair. It is a radiotherapy and chemotherapy sensitizer, especially in tumors sensitive to DNA alkylating agents (such as temozolomide). Moreover, KU 55933 inhibits phosphorylation of cytoplasmic AKT kinase, downregulates synthesis of cyclin D1 and induces cell cycle arrest in G1 phase.</p>

<p>Nafamostat is a broad-spectrum serine protease inhibitor produced by chemical synthesis. Nafamostat is effective through its antioxidant and anti-inflammatory activity. This drug is involved in inhibiting various enzyme systems such as coagulation and fibrinolytic systems.</p>

<p>Inhibits Jak kinases; immunosuppressive; anti-inflammatory</p>

<p>Potent inhibitor of phosphodiesterase type 9 (PDE9), tested in human and murine in vitro assays (IC50 values: 55 nM and 100 nM, respectively). BAY 73-6691 induces long-term potentiation and improves memory in rodents. BAY 73-6691 has been studied as a potential therapy for Alzheimer’s disease.</p>

<p>Cilastatin is a renal dehydropeptidase inhibitor, which is a compound sourced from synthetic processes designed to augment the pharmacokinetic profile of certain beta-lactam antibiotics. Its primary mode of action is to inhibit the enzyme dehydropeptidase I (DHP-I), located in the renal brush border. This enzyme typically degrades antibiotics, like imipenem, within the renal tubules. By inhibiting DHP-I, cilastatin prevents the inactivation of these antibiotics, thereby prolonging their active presence in the body and enhancing their antimicrobial efficacy.</p>

<p>Inhibitor of HIF prolyl hydroxylase</p>

<p>MAP kinase kinase (MEK) inhibitor. Binds to MEK-1, preventing phosphorylation and activation by Raf or MEK kinase. PD 098059 enhances self-renewal in stem cells. Has anti-growth and anti-proliferative effects on AML cells. Anti-apoptotic effect on AML cells observed in synergy with Nutlin-3a.</p>

<p>Potently inhibits PARP-1 and PARP-2 enzymes, orally bioavailable and crosses blood-brain barrier. Sensitises cancer cells to DNA-damaging chemotherapy and radiotherapy. Combination therapies investigated in clinical trials for solid and blood malignancies.</p>

<p>Cilastatin is a renal dehydropeptidase inhibitor drug that is used to prevent degradation of imipenem. It is used to treat a variety of infections in combination with imipenem. This drug blocks the mechanism of imipenem which is hydrolyzed by dehydropeptidase-I.</p>

<p>A potent, reversible and slow-binding inhibitor of delta-5 desaturases (D5Ds), by binding to the desaturase domain. Inhibiting D5D has therapeutic applications in inflammatory diseases. This is due to the increase in anti-inflammatory DGLA-derived eicosanoids and decrease in pro-inflammatory AA-derived eicosanoids.</p>

<p>Potent, selective and cell-permeable tool for modulation of O-GlcNAcylation. Ac4GlcNAcF3 is a dual modulator of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ac4GlcNAcF3 perturbates the GlcNAc cycling as OGT can incorporate GlcNAcF3 onto proteins but subsequently, it cannot be removed by OGA. In a mouse embryogenic fibroblast cell line, Ac4GlcNAcF3 increased the level of protein O-GlcNAcylation.</p>

<p>A prodrug of the DNA-intercalating agent daunorubicin with anti-tumoral activity, used for suicide gene therapy and activity-dependent ablation of cells. Daun02 is an inactive form of the toxin, which gets activated upon cleavage with prodrug-activating enzyme β-galactosidase, yielding daunorubicin. Genetic constructs have been designed carrying the lacZ gene, coding for β-galactosidase, under control of application-specific promoters. The cells expressing the β-gal undergo cell death since the enzyme hydrolizes the prodrug into the active toxin.</p>

<p>Sildenafil is a potent inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), consequently preventing the degradation of cGMP in the smooth muscle cells of the pulmonary vasculature and penis. For this reason Sildenafil can be used to increase blood flow, decrease inflammation and mucus production in the lungs and also can be used in the treatment of erectile dysfunction in men. This is largely due to the increased availability of cGMP which can cause the relaxation of the smooth muscles to be prolonged.</p>

<p>Selective and reversible inhibitor of the multicatalytic 26S proteasome. The inhibition of protein breakdown affects several metabolic pathways and leads to cell death. The compound is effective in treating multiple myeloma because it prevents the binding of myeloma cells to bone marrow stroma and inhibits osteoclast differentiation.</p>

<p>Ruxolitinib is a janus tyrosine kinase inhibitor active specifically on sub-types JAK1 and JAK2 with IC50 values in the nanomolar range. JAK1 and JAK2 are kinases involved in the regulation of hematopoiesis. Clinically applied to the treatment of intermediate and high-risk myelofibrosis, ruxolitinib is usually well tolerated by patients.</p>

<p>Inhibitor of myosin?II?specific ATPase which blocks the myosin heads in an actin-detached state, disrupts contractility of myosin-actin filaments and stabilizes super-relaxed state of muscle fibres. It inhibits skeletal muscle myosin, non-muscle myosin II and heart muscle myosin.</p>

<p>Cyclooxygenase inhibitor; anti-inflammatory; antipyretic; analgesic</p>

<p>Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) that has been used to treat pain and inflammation. Ketoprofen inhibits the production of inflammatory prostaglandins, which are released by platelets in response to injury or infection. The main mechanism of action is inhibition of cyclooxygenase enzymes COX 1 and COX 2 at the level of transcriptional activation. This results in decreased levels of prostaglandins that mediate pain, fever and inflammation.</p>

<p>PI3K/mTOR kinase inhibitor; anti-neoplastic</p>

<p>Neratinib is a protein kinase inhibitor that is used in the treatment of breast cancer. This drug binds to and inhibits EGFR, HER2 and HER4. As a result of this, it prevents autophosphorylation of tyrosine residues and reduces oncogenic signalling.</p>

<p>Inhibitor of FGFR kinase</p>

<p>Aurora kinase inhibitor</p>

<p>Activator of SIRT1 deacetylase</p>

<p>Inhibitor of cyclin dependend kinases</p>

<p>HMG-CoA reductase inhibitor</p>

<p>A potent and selective agonist of CCR4 chemokine receptor with IC50 values ranging from 10 to 25 nM across different species. CCR4 is involved in activation and migration of Th2 lymphocytes to the lungs in response to allergens. Treating sensitised rats results in reduced inflammation of lung tissue.</p>

<p>Sorafenib is a drug that belongs to the class of multikinase inhibitors. It inhibits a number of kinases, including the Mcl-1 protein, which is involved in apoptosis along with blocking picolinic acid (PA), an endogenous metabolite involved in apoptosis signal transduction. Sorafenib also binds to epidermal growth factor receptor (EGFR) on the surface of cancer cells, inhibiting the production of proteins that are required for angiogenesis, thus blocking the formation of new blood vessels. Sorafenib may also inhibit P-glycoprotein (Pgp) activity. Overall, these cytotoxic effects give Sorafenib anti-tumor properties, inhibiting angiogenesis and cellular transformation, which are the two main processes of tumor growth and metastasis. Sorafenib tosylate has been shown to be effective against a range of solid tumors such as breast, prostate and lung cancers and is also used for the treatment of metastatic colorectal cancer and renal cell carcinoma. A combination therapy group found that sorafenib was more effective when used with interferon alfa-2b for the treatment of advanced renal cell carcinoma. Sorafenib tosylate also has the potential for drug interactions with other drugs that are metabolized by cytochrome P450 enzymes.<br>Sorafenib tosylate is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>CBP/p300 histone acetyltransferase activator</p>

<p>EGFR tyrosine kinase inhibitor</p>

<p>Inhibits Wnt signaling pathway by targeting porcupine, a membrane-bound O-acyltransferase involved in the palmitoylation and secretion of Wnt. Anti-cancer properties of LGK 974 have been demonstrated in various tumor models of breast cancer, head and neck squamous cell carcinoma and glioblastoma. Blocks LPS-mediated inflammatory response in epithelial and endothelial cells.</p>

<p>A potent and selective inhibitor of cell death-inducing kinase RIP2 (IC50 = 5 nM). Reduces release of pro-inflammatory cytokines. Inhibits production of TNF-α and IL-6 in intestinal explants from patients with Crohn's disease and ulcerative colitis.</p>

<p>Fluvastatin is a statin that lowers blood cholesterol and triglycerides by inhibiting HMG-CoA reductase, an enzyme that plays a critical role in the synthesis of cholesterol. Fluvastatin has also been shown to reduce the incidence of myocardial infarction, and to reduce atherosclerotic lesions in animal models, reducing the incidence of cardiovascular disease. Fluvastatin also has been shown to inhibit the activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), which may be related to its anti-inflammatory effects. Furthermore, through lowering blood cholesterol, Fluvastatin also inhibits tubulointerstitial injury and prevents renal damage caused by high concentrations of the lipid.</p>

<p>A potent inhibitor of ubiquitin activating enzyme E1. Lowers ubiquitin conjugates in cells, thereby disrupting cell signalling, cell cycle progression and repair of DNA damage. Anti-tumor effects have been demonstrated in vitro and in vivo. TAK 243 has been used to study the biology of ubiquitins and its potential as anti-cancer therapy.</p>

<p>Selective inhibitor of the mutated RET variant RETV804M, which is the anticipated drug-resistant RET mutant that can occur in tumours treated with kinase inhibitors. The compound has a biochemical IC50 of 0.02 µM and selectivity for purified RETV804M over purified RET and KDR of 3.7 and 110, respectively. The efficacy of the compound was shown also in cell cultures with IC50 of 4.4 µM, and cell assay selectivity for RETV804M over RET and KDR of 0.89 and 2.3, respectively.</p>

<p>Anagrelide is a thrombocytopenic drug that is used to treat thrombocythemia and related conditions. This drug works by decreasing the platelet count by suppressing transcription factors that are necessary for the maturation of platelets. This drug is also a phosphodiesterase III inhibitor.</p>

<p>Inhibitor of MEK1/2 kinase enzymes; antineoplastic</p>

<p>Inhibitor of the histone methyltransferase SETD8 that supresses methylation of the K20 residue in histone 4. UNC 0379 treatment of human glioma reduced recruitment of 53BP1 protein to double strand breaks and sensitised cells to radiotherapy without altering cell cycle kinetics.</p>

<p>Inhibitor of aurora kinases</p>

<p>Inhibitor of protein kinase PKC</p>

<p>Pemetrexed is an antifolate drug that is used to treat mesothelioma and non-small cell lung cancer. It is used during chemotherapy and sometimes used in conjunction with cisplatin. This drug disrupts folate-dependent metabolic activities essential for cell replication. In vitro studies have shown that Pemetrexed inhibits thymidylate synthase.</p>