Mahindroo Neeraj, Wang Chiung-Chiu, Liao Chun-Chen, Huang Chien-Fu, Lu I-Lin, Lien Tzu-Wen, Peng Yi-Huei, Huang Wei-Jan, Lin Ying-Ting, Hsu Ming-Chen, Lin Chia-Hui, Tsai Chia-Hua, Hsu John T-A, Chen Xin, Lyu Ping-Chiang, Chao Yu-Sheng, Wu Su-Ying, Hsieh Hsing-Pang
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
J Med Chem. 2006 Feb 9;49(3):1212-6. doi: 10.1021/jm0510373.
A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARgamma protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARgamma protein resulting in potent activity.
描述了一系列新型基于吲哚的PPAR激动剂，从而发现了10k，一种高效的PPAR泛激动剂。结构生物学和分子对接研究表明，当配体与PPARγ蛋白结合时，酸性基团与连接体之间的距离对强效活性很重要。10k的疏水尾部与PPARγ蛋白产生强烈的疏水相互作用，从而产生强效活性。
