School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P. R. China.
J Med Chem. 2023 Jul 27;66(14):9251-9277. doi: 10.1021/acs.jmedchem.3c00390. Epub 2023 Jul 12.
Peptidyl-prolyl cis/trans isomerase family (PPIase) is structurally divided into three subfamilies, cyclophilins (Cyps), FK506-binding proteins (FKBPs), and parvulins. Pin1 belongs to the parvulin family and is the only enzyme capable of isomerizing the phosphorylated Ser/Thr-Pro motif (p-Ser/Thr-Pro) in its interacting proteins. Due to its multibiological functions in vivo, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis, Pin1 is extensively studied as a promising drug target for various human diseases, especially cancer. In this Perspective, we summarized the literature covering diverse classes of Pin1 inhibitors and the inhibition mechanism, aiming to provide insights for the design of potent Pin1 inhibitors and suggest alternative strategies for developing potent Pin1 inhibitors.
肽基脯氨酰顺反异构酶家族（PPIase）在结构上分为三个亚家族，亲环素（Cyps）、FK506 结合蛋白（FKBPs）和 parvulins。Pin1 属于 parvulin 家族，是唯一能够使相互作用蛋白中的磷酸化 Ser/Thr-Pro 基序（p-Ser/Thr-Pro）异构化的酶。由于其在体内的多种生物学功能，包括折叠、细胞内信号转导、转录、细胞周期进展和细胞凋亡，Pin1 被广泛研究作为治疗各种人类疾病，特别是癌症的有前途的药物靶点。在这篇观点文章中，我们总结了涵盖不同类别的 Pin1 抑制剂和抑制机制的文献，旨在为设计有效的 Pin1 抑制剂提供见解，并提出开发有效的 Pin1 抑制剂的替代策略。
