Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage
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 cascad...
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| Format: | Article |
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Elsevier
2020
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| _version_ | 1796962088074084352 |
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| author | Wang, Hao Chen, Meiling Sang, Xiaohong You, Xuefu Wang, Yucheng Paterson, Ian Charles Hong, Wei Yang, Xinyi |
| author_facet | Wang, Hao Chen, Meiling Sang, Xiaohong You, Xuefu Wang, Yucheng Paterson, Ian Charles Hong, Wei Yang, Xinyi |
| author_sort | Wang, Hao |
| collection | UM |
| description | 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 |
| first_indexed | 2024-03-06T06:03:42Z |
| format | Article |
| id | um.eprints-24767 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T06:03:42Z |
| publishDate | 2020 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | um.eprints-247672020-06-10T01:08:20Z http://eprints.um.edu.my/24767/ Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage Wang, Hao Chen, Meiling Sang, Xiaohong You, Xuefu Wang, Yucheng Paterson, Ian Charles Hong, Wei Yang, Xinyi R Medicine TP Chemical technology 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 Elsevier 2020 Article PeerReviewed Wang, Hao and Chen, Meiling and Sang, Xiaohong and You, Xuefu and Wang, Yucheng and Paterson, Ian Charles and Hong, Wei and Yang, Xinyi (2020) Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage. European Journal of Medicinal Chemistry, 191. p. 112154. ISSN 0223-5234, DOI https://doi.org/10.1016/j.ejmech.2020.112154 <https://doi.org/10.1016/j.ejmech.2020.112154>. https://doi.org/10.1016/j.ejmech.2020.112154 doi:10.1016/j.ejmech.2020.112154 |
| spellingShingle | R Medicine TP Chemical technology Wang, Hao Chen, Meiling Sang, Xiaohong You, Xuefu Wang, Yucheng Paterson, Ian Charles Hong, Wei Yang, Xinyi Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title | Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title_full | Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title_fullStr | Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title_full_unstemmed | Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title_short | Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage |
| title_sort | development of small molecule inhibitors targeting tgf β ligand and receptor structures mechanism preclinical studies and clinical usage |
| topic | R Medicine TP Chemical technology |
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