GW9662在PPARγ上结合Cys(285),PPARγ是三种PPAR中保守的。GW9662是PPARγ拮抗剂,用于抑制脂肪细胞分化。GW9662抑制PPARγ激活,且抑制人乳腺癌肿瘤细胞系(MCF7, MDA-MB-468, MDA-MB-231)生长,IC50为20 μM-30 μM,说明 GW9662的PPARγ激动剂性能或PPARγ非依赖性生长抑制机制。Rosiglitazone(50 μM)与GW9662(10 μM)联用,作用于MDA-MB-231细胞,7天后,统计学上产生较低的存活细胞数。在原代鼠骨髓(BMs)和RAW264.7细胞中,PPARγ1配体能够抑制RANKL诱导的破骨细胞形成。重要的是,GW 9662(2 μM)可逆转这些配体的抑制作用,存在浓度依赖性。GW 9662(2 μM)作用于BMs,阻断IL-4对破骨细胞形成的抑制。GW 9662(1 μM) 作用于RAW264.7细胞,抑制NF-κB的RANKL激活。GW9662(10 μM)作用于甲状腺眼病患者的原代前脂肪细胞,抑制激素和激动剂诱导的脂肪细胞分化。
A cell-permeable, selective and irreversible PPARγ antagonist (IC50 = 3.3 nM, 32 nM, and 2 μM for PPARγ, PPARα, and PPARδ, respectively). Reported to covalently modify a cysteine residue in the bindin g site of PPAR. At a concentration of 10 μM, also acts as an agonist of human pregnane X receptor (PXR) and farnesoid X receptor (FXR). Does not activate liver X receptor-a (LXRa), retinoic acid recep tor (RAR), retinoid X receptor-a (RXRa) and thyroid receptors a and b (TRa and TRb).