Enzyme Modulators

<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>