Imiglitazar (TAK-559)
(Synonyms: TAK-559) 目录号 : GC32521
Imiglitazar (TAK-559) (TAK559) 是一种有效的双重人类 PPARα;和 PPARγ1 激动剂,EC50 值为 67 和 31 nM。
Cas No.:250601-04-8
Sample solution is provided at 25 µL, 10mM.
Imiglitazar (TAK559) is a potent and dual human PPARα and PPARγ1 agonist with EC50 values of 67 and 31 nM.
TAK-559 is a partial agonist for hPPARg1 with about 68% of maximal activation obtained with rosiglitazone, a known PPARγ agonist. PPARy is significantly activated at a high concentration (10 μM) of TAK-559. Competition-binding assays using radiolabeled ligand indicates that the transactivation of all hPPAR subtypes by TAK-559 is due to direct binding of TAK-559 to each subtype. TAK-559 also recruit the coactivator SRC-1 to each of hPPARγ1 and hPPARα, and to dissociate the corepressor NCoR from each of hPPARγ1 and hPPARα[1].TNFα- or IL-1β-induced THP-1 cell attachment to cultured endothelial cells is significantly reduced in the presence of 10 μM TAK-559. The secretion of monocyte chemoattractant protein-1 (MCP-1) from endothelial cells is reduced by 36% in the presence of 10 μM TAK-559, accompanied with the decreased mRNA expression in the cells. The proliferation and migration of cultured smooth muscle cells are significantly decreased in the presence of TAK-559[2].
TAK-559 treatment results in significant elevation of circulating high-density lipoprotein (HDL) cholesterol levels, consisting of an increase in large HDL particles and a decrease in small dense HDL particles. Plasma triglyceride and apolipoprotein B-100 levels decrease, whereas apolipoprotein A-I increasesduring TAK-559 treatment. Hyperinsulinemia and insulin resistance are significantly corrected with the highest dose of 3.0 mg/kg per day in these prediabetic monkeys. In addition, no adverse effects on representative liver function parameters are observed during the study period[3].
[1]. Sakamoto J, et al. A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26. [2]. Seki N, et al. A potent activator of PPARalpha and gamma reduces the vascular cell recruitment and inhibits the intimal thickning in hypercholesterolemic rabbits. Atherosclerosis. 2005 Jan;178(1):1-7. [3]. Ding SY, et al. A novel peroxisome proliferator--activated receptor alpha/gamma dual agonist ameliorates dyslipidemia and insulin resistance in prediabetic rhesus monkeys. Metabolism. 2007 Oct;56(10):1334-9.
Kinase experiment: | Competition binding assays are performed with cell extract containing hPPARδ and 20 nM [3H]L-783483 in the presence of indicated concentrations of TAK-559 (1, 10, 100 μM) or Iloprost. Data are expressed as the percentage of specific binding in the absence of competitor (vehicle (V) (1% DMSO))[1]. |
Cell experiment: | COS-1 cells are cotransfected with expression plasmid for full-length hPPARγ1 as a VP16 fusion protein, GAL4-SRC-1 (A) or GAL4-NcoR (B) expression plasmid and (UAS)5-tk-Luciferase reporter plasmid. Cells are cultured in the presence of TAK-559 (0.01, 0.1, 1 μM) or rosiglitazone for 2 days. The cell extracts are assayed for luciferase activity[1]. |
References: [1]. Sakamoto J, et al. A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26. |
Cas No. | 250601-04-8 | SDF | |
别名 | TAK-559 | ||
Canonical SMILES | CC(OC(C1=CC=CC=C1)=N2)=C2COC(C=C3)=CC=C3CO/N=C(CCC(O)=O)/C4=CC=CC=C4 | ||
分子式 | C28H26N2O5 | 分子量 | 470.52 |
溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
1 mM | 2.1253 mL | 10.6265 mL | 21.2531 mL |
5 mM | 0.4251 mL | 2.1253 mL | 4.2506 mL |
10 mM | 0.2125 mL | 1.0627 mL | 2.1253 mL |
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