School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, China.
State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, Shandong, China.
Mini Rev Med Chem. 2020;20(11):1017-1030. doi: 10.2174/1389557520666200303130833.
Protein tyrosine phosphatase 2 (SHP-2) has long been proposed as a cancer drug target. Several small-molecule compounds with different mechanisms of SHP-2 inhibition have been reported, but none are commercially available. Pool selectivity over protein tyrosine phosphatase 1 (SHP-1) and a lack of cellular activity have hindered the development of selective SHP-2 inhibitors. In this review, we describe the binding modes of existing inhibitors and SHP-2 binding sites, summarize the characteristics of the sites involved in selectivity, and identify the suitable groups for interaction with the binding sites.
蛋白酪氨酸磷酸酶 2（SHP-2）长期以来一直被提议作为癌症药物靶点。已经报道了几种具有不同 SHP-2 抑制机制的小分子化合物，但没有一种可商业化。对蛋白酪氨酸磷酸酶 1（SHP-1）的池选择性和缺乏细胞活性阻碍了选择性 SHP-2 抑制剂的发展。在这篇综述中，我们描述了现有抑制剂和 SHP-2 结合位点的结合模式，总结了参与选择性的位点的特征，并确定了与结合位点相互作用的合适基团。
