Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage
Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage
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TGF-β配体和受体小分子抑制剂的开发：结构、机制、临床前研究和临床应用
DOI：
10.1016/j.ejmech.2020.112154
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发表时间：
2020-04-01
影响因子：
6.7
通讯作者：
Yang, Xinyi
中科院分区：
文献类型：
--
作者：
Wang, Hao;Chen, Meiling;Yang, Xinyi
转化生长因子-β（TGF-β）是调节多种细胞过程如生长、发育和分化的多效性蛋白超家族的成员。在与I型和II型TGF-β丝氨酸/苏氨酸激酶受体结合后，TGF-β激活涉及SMAD依赖性和非依赖性途径的下游信号级联。异常的TGF-β信号传导与多种疾病相关，例如纤维化、心血管疾病和癌症。因此，TGF-β信号通路被认为是潜在的药物靶点。已经设计并开发了各种有机分子作为TGF-β信号传导途径抑制剂，并且它们通过下调TGF-β的表达或通过抑制TGF-β受体的激酶活性来发挥作用。在这篇综述中，我们讨论了有机分子作为TGF-β抑制剂的研究现状，重点是市场上或临床或临床前开发阶段的化合物的生物学功能和结合姿势。(c)2020 Elsevier Masson SAS。All rights reserved.
Transforming growth factor-beta (TGF-beta) 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-beta serine/threonine kinase receptors, TGF-beta activates downstream signaling cascades involving both SMAD-dependent and -independent pathways. Aberrant TGF-beta signaling is associated with a variety of diseases, such as fibrosis, cardiovascular disease and cancer. Hence, the TGF-beta signaling pathway is recognized as a potential drug target. Various organic molecules have been designed and developed as TGF-beta signaling pathway inhibitors and they function by either down-regulating the expression of TGF-beta or by inhibiting the kinase activities of the TGF-beta receptors. In this review, we discuss the current status of research regarding organic molecules as TGF-beta 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. (c) 2020 Elsevier Masson SAS. All rights reserved.