School of Pharmacy, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China.
School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan, 750021, China; Key Laboratory of Chemical Engineering and Technology, State Ethnic Affairs Commission, North Minzu University, Yinchuan, 750021, China.
Eur J Med Chem. 2020 Apr 1;191:112154. doi: 10.1016/j.ejmech.2020.112154. Epub 2020 Feb 18.
Transforming growth factor-β (TGF-β) is a member of a superfamily of pleiotropic proteins that regulate multiple cellular processes such as growth, development and differentiation. Following binding to type I and II TGF-β serine/threonine kinase receptors, TGF-β activates downstream signaling cascades involving both SMAD-dependent and -independent pathways. Aberrant TGF-β signaling is associated with a variety of diseases, such as fibrosis, cardiovascular disease and cancer. Hence, the TGF-β signaling pathway is recognized as a potential drug target. Various organic molecules have been designed and developed as TGF-β signaling pathway inhibitors and they function by either down-regulating the expression of TGF-β or by inhibiting the kinase activities of the TGF-β receptors. In this review, we discuss the current status of research regarding organic molecules as TGF-β inhibitors, focusing on the biological functions and the binding poses of compounds that are in the market or in the clinical or pre-clinical phases of development.
转化生长因子-β（TGF-β）是一多效蛋白超家族的成员，可调节多种细胞过程，如生长、发育和分化。TGF-β与 I 型和 II 型 TGF-β丝氨酸/苏氨酸激酶受体结合后，激活下游信号转导级联反应，涉及 SMAD 依赖性和非依赖性途径。TGF-β信号异常与多种疾病有关，如纤维化、心血管疾病和癌症。因此，TGF-β信号通路被认为是一个潜在的药物靶点。已经设计和开发了各种有机分子作为 TGF-β信号通路抑制剂，它们通过下调 TGF-β的表达或抑制 TGF-β受体的激酶活性来发挥作用。在这篇综述中，我们讨论了作为 TGF-β抑制剂的有机分子的研究现状，重点介绍了已上市或处于临床或临床前开发阶段的化合物的生物学功能和结合构象。
