CAS NO. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. NDI-091143 is a potent inhibitor of human ATP-citrate lyase(ACLY) with a Ki of 7.0 nM and an IC50 of 2.1 nM in the ADP-Glo assay. ATP-citrate lyase (ACLY) is a cytosolic enzyme that catalyzes the generation of acetyl CoA from citrate. Hatzivassiliou G, et al. The same treatments also reduce in vivo tumor growth and induce differentiation. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. ATP citrate lyase (ACL) inhibitor (IC 50 = 0.13 μ M for human recombinant ACL); blocks lipid synthesis (IC 50 = 8 μ M in HepG2 cells). Carlotta Granchi, ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism, European Journal of Medicinal Chemistry, 10.1016/j.ejmech.2018.09.001, 157, (1276-1291), (2018). Orally bioavailable. Antimycins, inhibitors of ATP-citrate lyase, from a Streptomyces sp. This chart is created by aggregating the total number of claims for the drugs in this class divided by the # of drugs with a specific indication. ATP-citrate lyase (ACLY) catalyzes the ATP-dependent conversion of citrate and CoA to oxaloacetate and acetyl-CoA. 50 mg: $300.00. 1. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis. Studies were performed with recombinant human ACL to ascertain the nature of the catalytic phosphorylation that initiates the ACL reaction and the identity of the active site residues involved. Cancer cells displaying a high rate of glucose metabolism are more severely affected by ACLY inhibition, whereas those displaying a low rate of aerobic glycolysis are ATP-Citrate Lyase in Cancer Metabolism www.aacrjournals.org Cancer Res; 72(15) August 1, 2012 3711 ATP citrate lyase inhibition can suppress tumor cell growth. The enzyme is a tetramer of apparently identical subunits. Why are ACL Inhibitors prescribed? Zaidi N, Swinnen JV, Smans K (2012) ATP-citrate lyase: a key player in cancer metabolism. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. ATP citrate lyase knockdown impacts cancer stem cells in vitro. ATP citrate lyase is primarily expressed in lipogenic tissues. Availability: In stock. The activated substance inhibits ATP citrate lyase, which is involved in the liver's biosynthesis of cholesterol upstream of HMG-CoA reductase, the enzyme that is blocked by statins.. ATP citrate lyase inhibitors such as bempedoic acid lower LDL cholesterol by the same mechanism of action as statins and may provide similar or perhaps additive cardiovascular protection. Bempedoic acid (ETC-1002), a novel therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits ATP citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Interestingly, ACLY is a strategic enzyme linking both the glycolytic and lipidic metabolism. The acetyl-CoA product is crucial for fatty acid metabolism, cholesterol biosynthesis, and post-translational modification of proteins (acetylation and prenylaion). 100 mg: $480.00. This study aimed to … Methods of inducing apoptosis in cancer cells using an ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. Technical Data. NDI-091143 is a potent and high-affinity human ATP-citrate lyase (ACLY) inhibitor with an IC 50 of 2.1 nM (ADP-Glo assay), a K i of 7.0 nM and a K d of 2.2 nM. Methods of treating individuals identified as having cancer using ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. Although rodent studies suggested potential effects of ACL inhibition on both fatty acid and cholesterol synthesis, studies in humans show an effect only on cholesterol synthesis. Lipid Metabolism; Literature in this Area. High Cholesterol (100%) High Cholesterol. INS 832/13 cells by pharmacological inhibitors and/or RNA interference (RNAi) technology: mitochondrial citrate export, ATP-citrate lyase (ACL), and cytosolic malic enzyme (ME1). ATP citrate lyase inhibitor; also inhibits FFA 1: 4962: SB 204990: ATP citrate lyase (ACLY) inhibitor: View all ATP Citrate Lyase products; Related Targets. Acetyl CoA is a vital building block for the endogenous biosynthesis of fatty acids and cholesterol and is involved in isoprenoid-based protein modifications. ATP citrate lyase (ACLY), a key enzyme in the metabolic reprogramming of many cancers, is widely expressed in various mammalian tissues. Displays no cytotoxicity up to a concentration of 50 μ M. Lowers plasma glucose and triglycerides in a mouse model of hyperlipidemia. substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. It is one of the major sources of cytosolic acetyl-CoA, and is a central metabolic enzyme. Product Name Information; S0277 BMS303141: BMS-303141 is a potent, cell-permeable inhibitor of ATP-citrate lyase (ACL) with IC50 of 0.13 μM. ACL (ATP Citrate Lyase) Inhibitors are used to treat high cholesterol. 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