Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Med Chem. 2010 Mar 25;53(6):2661-5. doi: 10.1021/jm901798e.
Insulin-like growth factor-1 receptor (IGF-1R) is a growth factor receptor tyrosine kinase acting as a critical mediator of cell proliferation and survival. Novel 5-benzylidenethiazolidine-2,4-dione (5) and 5-(furan-2-ylmethylene)thiazolidine-2,4-dione (6) compounds were identified as potent and selective IGF-1R inhibitors via hierarchical virtual screening. Initial SAR and biological activity of the analogues of 5 and 6 with thiazolidine-2,4-dione template are presented, and several inhibitors with low nanomolar potency are reported.
胰岛素样生长因子-1 受体 (IGF-1R) 是一种生长因子受体酪氨酸激酶，作为细胞增殖和存活的关键介质发挥作用。通过层次虚拟筛选，鉴定出新型 5-亚苄基噻唑烷-2,4-二酮 (5) 和 5-(呋喃-2-基亚甲基)噻唑烷-2,4-二酮 (6) 化合物，它们是有效的、选择性的 IGF-1R 抑制剂。本文介绍了噻唑烷-2,4-二酮模板类似物 5 和 6 的初始 SAR 和生物学活性，并报道了几种具有低纳摩尔效力的抑制剂。
