ATP-citrate lyase (ACLY) is an enzyme that links glycolysis to lipid metabolism. ATP Citrate Lyase Inhibitors as Novel Cancer Therapeutic Agents. Keywords:ACL inhibitors, ATP citrate lyase, cancer therapy, citrate, lipogenesis, small chemicals. ATP citrate lyase (ACLY) is a cytosolic homotetrameric enzyme that catalyzes the conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate, with the simultaneous hydrolysis of ATP to ADP and phosphate. 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 Lipid Metabolism; Literature in this Area. M.Wt: 424.3. The acetyl-CoA product is crucial for fatty acid metabolism, cholesterol biosynthesis, and post-translational modification of proteins (acetylation and prenylaion). ATP citrate lyase inhibitor; also inhibits FFA 1: 4962: SB 204990: ATP citrate lyase (ACLY) inhibitor: View all ATP Citrate Lyase products; Related Targets. ATP citrate lyase knockdown impacts cancer stem cells in vitro. 2013;4:e696. ATP citrate lyase inhibition can suppress tumor cell growth. BMS303141 inhibits lipid synthesis in HepG2 cells with an IC50 of 8 μM, and lowers plasma triglycerides in a murine hyperlipdemia model. substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. Abstract:ATP citrate lyase (ACL or ACLY) is an extra-mitochondrial enzyme widely distributed in various human and animal tissues. ATP citrate lyase (ACL) catalyzes an ATP-dependent biosynthetic reaction which produces acetyl-coenzyme A and oxaloacetate from citrate and coenzyme A (CoA). Methods of inducing apoptosis in cancer cells using an ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. To date only partial X-ray structures of ACLY have been solved, thus limiting the design of novel inhibitors. Bempedoic acid is a prodrug.It is activated to the thioester with coenzyme A by the enzyme SLC27A2 in the liver. 25 mg: $160.00. 943962-47-8. 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. They work in the liver to inhibit the biosynthesis of cholesterol. ATP-citrate lyase (ACLY) catalyzes the ATP-dependent conversion of citrate and CoA to oxaloacetate and acetyl-CoA. The same treatments also reduce in vivo tumor growth and induce differentiation. Cancer Cell. 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). ATP citrate lyase (ACLY), a key enzyme in the metabolic reprogramming of many cancers, is widely expressed in various mammalian tissues. Source; PubMed; Authors: Xu-Yu Zu. 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. It is one of the major sources of cytosolic acetyl-CoA, and is a central metabolic enzyme. The anti-mycins were first isolated from a Streptomyces sp. ATP citrate lyase is an important enzyme for he fast dividing cancer cells ATP citrate lyase (ACL or ACLY) is an intracellular enzyme (located in cytosol) responsible for the conversion of citrate that comes out of the mitochondria, to acetyl-CoA and oxaloacetate. 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. BMS-303141 shows inhibition of total lipid syntheses with IC50 of 8 μM in HepG2 cells. Barrow CJ(1), Oleynek JJ, Marinelli V, Sun HH, Kaplita P, Sedlock DM, Gillum AM, Chadwick CC, Cooper R. Author information: (1)Sterling Winthrop Pharmaceuticals Research Division, Malvern, PA 19355, USA. Availability: In stock. Knowles LM, Yang C, Osterman A, … Acetyl CoA is a vital building block for the endogenous biosynthesis of fatty acids and cholesterol and is involved in isoprenoid-based protein modifications. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis. Hatzivassiliou G, et al. BMS303141 Chemical Structure. ATP-citrate lyase (ACLY) is a cytosolic enzyme that catalyzes the generation of acetyl CoA from citrate. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. 50 mg: $300.00. Orally bioavailable. Interestingly, ACLY is a strategic enzyme linking both the glycolytic and lipidic metabolism. (Mg. citrate).2) In the course of screening for other ATP-citrate lyase inhibitors we isolated a series of antimycins which also inhibit the substrate Mg. citrate. 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. Bempedoic acid (BA; ETC-1002) is a new agent that reduces cholesterol synthesis through inhibition of adenosine triphosphate citrate lyase, an enzyme upstream from 3-hydroxy-3-methylglutaryl-coenzyme A.In animal models, BA also influences fatty acid synthesis, but in humans, its role is limited primarily to lowering low-density lipoprotein cholesterol (LDL-C). Crossref. 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. 1. 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). Technical Data. ATP-citrate lyase inhibitor. ATP citrate lyase (ACL or ACLY) is an extra-mitochondrial enzyme widely distributed in various human and animal 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. Zaidi N, Swinnen JV, Smans K (2012) ATP-citrate lyase: a key player in cancer metabolism. Methods of treating individuals identified as having cancer using ATP citrate lyase inhibitor and/or tricarboxylate transporter inhibitor are disclosed. In the liver and recognition of citrate and CoA with a concomitant hydrolysis of ATP to ADP phosphate! Displaying aerobic glycolysis stem cells in vitro as having cancer using ATP citrate lyase ( ACLY ) is an enzyme. 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