Sawyer J Scott, Anderson Bryan D, Beight Douglas W, Campbell Robert M, Jones Michael L, Herron David K, Lampe John W, McCowan Jefferson R, McMillen William T, Mort Nicholas, Parsons Stephen, Smith Edward C R, Vieth Michal, Weir Leonard C, Yan Lei, Zhang Faming, Yingling Jonathan M
Discovery Chemistry Research and Technology, The Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
J Med Chem. 2003 Sep 11;46(19):3953-6. doi: 10.1021/jm0205705.
Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAR in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.
本文描述了基于吡唑的转化生长因子-β I型受体激酶结构域（TbetaR-I）抑制剂。通过基于酶和细胞的体外试验对构效关系进行研究，结果出现了两个亚系列，它们对p38丝裂原活化蛋白激酶具有不同的选择性。通过将强效抑制剂与TbetaR-I受体激酶结构域成功共结晶并进行X射线分析，确定了其在活性位点的共同结合模式。
