Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage
Document Type
Article
Publication Date
1-1-2020
Abstract
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. © 2020 Elsevier Masson SAS
Keywords
TGF-β, TGF-β receptor, SMAD signaling pathway, Small-molecule inhibitor
Divisions
Dentistry
Funders
National Natural Science Foundation of China ( 81660588 , 81960623 , 81773582 , 81973383 , 8132100 , 81621064 ),Key R&D Program of Ningxia ( 2018BFG02004 ),Program for Leading Talents of Ningxia Province ( KJT2018004 ),National Mega-project for Innovative Drugs ( 2019ZX09721001 ),National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China ( 2019ZX09201001-003-007 ),CAMS Initiative Fund for Innovative Medicine ( 2016-I2M-3-014 ),Peking Union Medical College Youth Fund (PUMC) ( 33320140177 and 3332016139 )
Publication Title
European Journal of Medicinal Chemistry
Volume
191
Publisher
Elsevier