Zhang Guobao, Ren Pingda, Gray Nathanael S, Sim Taebo, Wang Xia, Liu Yi, Che Jianwei, Dong Weitong, Tian Shin-Shay, Sandberg Mark L, Spalding Tracy A, Romeo Russell, Iskandar Maya, Wang Zhiliang, Seidel H Martin, Karanewsky Donald S, He Yun
Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6691-5. doi: 10.1016/j.bmcl.2009.09.123. Epub 2009 Oct 12.
A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs.
设计了一系列4-氨基-6-苯并咪唑嘧啶，以靶向淋巴细胞特异性酪氨酸激酶（Lck），它是Src家族激酶（SFKs）的成员之一。这些II型抑制剂通过细胞Lck依赖性增殖试验进行了优化，能够在个位数纳摩尔浓度下抑制Lck。这种骨架可能为开发多种SFKs的强效抑制剂提供有价值的模板。
