Ma Liang, Wang Taijin, Shi Min, Ye Haoyu
Department of Nephrology, Kidney Research Institute, West China Medical School of Sichuan University, Chengdu, People's Republic of China.
State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, People's Republic of China.
Drug Des Devel Ther. 2016 May 30;10:1807-15. doi: 10.2147/DDDT.S106406. eCollection 2016.
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC50) 0.75±0.20 μM, exhibited in vitro potency comparable with a 0.83±0.14 μM of the positive control rosiglitazone. Molecular docking and molecular dynamics simulations indicated that phenylthiazole acid 4t interacted with the amino acid residues of the active site of the PPARγ complex in a stable manner, consistent with the result of the in vitro ligand assay.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体介导的转录因子，在葡萄糖和脂质稳态中起关键作用，PPARγ配体在这些以及其他领域具有治疗潜力。在本研究中，合成了一系列苯基噻唑酸，并通过基于荧光偏振的便捷PPARγ配体筛选试验评估了其激动活性。化合物4t作为一种潜在的PPARγ激动剂，半数最大有效浓度（EC50）为0.75±0.20 μM，其体外效力与阳性对照罗格列酮的0.83±0.14 μM相当。分子对接和分子动力学模拟表明，苯基噻唑酸4t以稳定的方式与PPARγ复合物活性位点的氨基酸残基相互作用，这与体外配体试验的结果一致。
