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GSK3787

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Chemical Structure| 188591-46-0 同义名 : -
CAS号 : 188591-46-0
货号 : A575893
分子式 : C15H12ClF3N2O3S
纯度 : 99%+
分子量 : 392.781
MDL号 : MFCD00099612
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(127.3 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • PPARβ/δ

    PPARδ, pIC50:6.6

  • PPARδ

    PPARδ, pIC50:6.6
描述 The peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors belonging to the nuclear receptor superfamily and play key roles in multiple physiological pathway. Three PPAR receptor subtypes, designated as PPARα, PPARγ, and PPARδ, have been identified. PPARδ is recognized as a regulator of genes involved in fatty acid oxidation, reverse cholesterol transport, and carbon substrate utilization in skeletal muscle. GSK3787 is a potent and selective antagonist for PPARδ with pIC50 value of 6.6 in ligand displacement assay. GSK3787 completely antagonized the activity of PPARδ agonist 1 with a pIC50 of 6.9. GSK3787 was administered to human skeletal muscle cells at various doses and found to effectively antagonize the gene expression of CPT1a. This suggests that GSK3787 may selectively block the basal activity of the receptor on some PPARδ target genes highlighting the potential utility of this compound as a useful tool for further elucidating the biological role of PPARδ. GSK3787 was administered intravenously (0.5 mg/kg) and orally (10 mg/kg) to male C57BL/6 mice. Mean clearance (CL) and volume of distribution at steady state (Vss) following iv administration were 39 ± 11 (mL/min)/kg and 1.7 ± 0.4 L/kg, respectively. Following oral administration, good exposure (Cmax = 881 ± 166 ng/mL, AUCinf = 3343 ± 332 hng/mL), half-life (2.7 ± 1.1 h), and bioavailability (F = 77 ± 17%) were observed. Thus, GSK3787 has pharmacokinetic properties suitable for use as an in vivo PPARδ antagonist tool compound in mice[1].
作用机制 GSK3787 covalently modifies Cys249 within the ligand binding pocket[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.55mL

0.51mL

0.25mL

12.73mL

2.55mL

1.27mL

25.46mL

5.09mL

2.55mL
参考文献

[1]Shearer BG, Wiethe RW, Ashe A, et al. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 2010;53(4):1857-1861.

[2]Palkar PS, Borland MG, et al. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787. Mol Pharmacol. 2010 Sep;78(3):419-30.