Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B
Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B
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DOI：
10.1002/med.20079
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发表时间：
2007-07-01
影响因子：
13.3
通讯作者：
Wan, Qian
中科院分区：
文献类型：
--
作者：
Lee, Seokjoon;Wan, Qian
蛋白酪氨酸磷酸酶（PTP）是信号酶大家族，通过调节细胞内酪氨酸磷酸化水平，控制细胞生长和分化、代谢、细胞迁移、基因转录、离子通道活性、免疫反应、细胞凋亡和骨骼发育，在细胞内信号转导中发挥重要作用。在所有 PTP 中，蛋白酪氨酸磷酸酶 1B (PTP1B) 在细胞信号转导和许多人类疾病（包括癌症、糖尿病和肥胖症）中发挥着重要作用。因此，PTP1B 的小分子抑制剂可能是有前途的候选药物。由于许多 PTP 家族的结构同源性，寻找针对每个 PTP 的特异性抑制剂是一项具有挑战性的任务。最近的研究表明，应利用保守活性位点周围的次级结合袋或外周结合位点来设计新型有效且选择性的 PTP1B 抑制剂。在这篇综述中，我们讨论了小分子 PTP1B 特异性抑制剂的结构和生物学特征，特别强调了针对 PTP1B 的小分子抑制剂，而不是过去 4 年合成的其他 PTP。 (c) 2006 年 Wiley 期刊公司
Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play essential roles in intracellular signal transduction by regulating the cellular level of tyrosine phosphorylation to control cell growth and differentiation, metabolism, cell migration, gene transcription, ion-channel activity, immune response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many human diseases, including cancer, diabetes, and obesity. Therefore, small molecular inhibitors of PTP1B can be promising drug candidates. Because of the structural homologies in many families of PTPs, it is a challenging task to find inhibitors specific to each PTP. Recent studies suggested that secondary binding pockets or peripheral binding sites around the conserved active site should be exploited to design novel potent and selective PTP1B inhibitors. In this review, we discuss the structural and biological features of small molecular PTP1B-specific inhibitors, with particular emphasis on small molecular inhibitors targeting PTP1B over the other PTPs thathavebeen synthesized in the past 4 years. (c) 2006 Wiley Periodicals, Inc.