Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage

被引：40
作者：
Wang, Hao [1 ,2 ]
Chen, Meiling [3 ,4 ]
Sang, Xiaohong [5 ]
You, Xuefu [5 ]
Wang, Yucheng [5 ]
Paterson, Ian C. [6 ,7 ]
Hong, Wei [3 ,4 ]
Yang, Xinyi [5 ]
机构：
[1] Minzu Univ China, Sch Pharm, Beijing 100081, Peoples R China
[2] Minzu Univ China, Minist Educ, Key Lab Ethnomed, Beijing 100081, Peoples R China
[3] North Minzu Univ, Sch Chem & Chem Engn, Yinchuan 750021, Ningxia, Peoples R China
[4] North Minzu Univ, Key Lab Chem Engn & Technol, State Ethn Affairs Commiss, Yinchuan 750021, Ningxia, Peoples R China
[5] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Lab Pharmacol, Beijing Key Lab Antimicrobial Agent, Beijing 100050, Peoples R China
[6] Univ Malaya, Fac Dent, Dept Oral & Craniofacial Sci, Kuala Lumpur 50603, Malaysia
[7] Univ Malaya, Fac Dent, Oral Canc Res & Coordinating Ctr, Kuala Lumpur 50603, Malaysia
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 191卷
基金：
中国国家自然科学基金;
关键词：
TGF-beta; TGF-beta receptor; SMAD signaling pathway; Small-molecule inhibitor; GROWTH-FACTOR-BETA; I KINASE INHIBITOR; EPITHELIAL-MESENCHYMAL TRANSITION; TRANSFORMING GROWTH-FACTOR-BETA-1; PULMONARY INFLAMMATION; LY2157299; MONOHYDRATE; EXTRACELLULAR-MATRIX; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY; ALK5; INHIBITOR;
D O I：
10.1016/j.ejmech.2020.112154
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
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页数：11
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