| Description | GW6471 is a selective PPARα antagonist (IC50=0.24 μM) that enhances the binding affinity of the PPARα ligand-binding domain to the co-inhibitory proteins SMRT and NCoR. GW6471 has antitumor activity, inhibiting cell proliferation and inducing apoptosis. |
| In vitro | 方法：RCC 细胞 Caki-1 (VHL 野生型) 和 786-O (VHL 突变型) 用 GW6471 (12.5-100 µM) 处理 72 h，使用 MTT assay 检测细胞活力。结果：GW6471 在两种细胞系中显著且剂量依赖性地抑制细胞活力，高达约 80%。[1]方法：正常上皮细胞 NHK 和 RCC 细胞 Caki-1、786-O 用 GW6471 (25 µM) 处理 24 h，使用 Western Blot 检测靶点蛋白表达水平。 结果：在与 GW6471 孵育 24 h 后，c-Myc 在 NHK 细胞中显示出蛋白质水平增加的趋势，而在两种 RCC 细胞系中都显示出显著降低的趋势。[2] |
| In vivo | 方法：为检测体内抗肿瘤活性，将 GW6471 (20 mg/kg) 腹腔注射给携带 RCC 肿瘤 Caki-1 的 Nu/Nu 小鼠，每两天一次，持续四周。结果：PPARα 拮抗剂 GW6471 对异种移植小鼠模型的体内处理减弱了 RCC 的生长。[2] |
| Synonyms | GW 6471 |
| molecular weight | 619.67 |
| Molecular formula | C35H36F3N3O4 |
| CAS | 880635-03-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 16.67 mg/mL (26.9 mM), Sonication is recommended. |
| References | 1. Abu Aboud O, et al. Inhibition of PPARα induces cell cycle arrest and apoptosis, and synergizes with glycolysis inhibition in kidney cancer cells. PLoS One. 2013 Aug 7;8(8):e71115. 2. Abu Aboud O, et al. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C890-8. 3. Abu Aboud O, et al. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C890-8. |
| Citations | 1. Wang R, Zhao J, Jin J, et al. WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC. Lipids in Health and Disease. 2022, 21(1): 1-18. |