Research progresses of small molecule inhibitors targeting TGF-β and its receptors
10.16438/j.0513-4870.2019-0132
- VernacularTitle:靶向TGF-β及受体的小分子抑制剂研究进展
- Author:
Xiao-hong SANG
1
;
Hao WANG
2
;
Xue-fu YOU
1
;
Xin-yi YANG
1
Author Information
1. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China
- Publication Type:Research Article
- Keywords:
TGF-β;
TGF-β receptor;
Smad signaling pathway;
small-molecule inhibitor
- From:
Acta Pharmaceutica Sinica
2019;54(9):1538-1546
- CountryChina
- Language:Chinese
-
Abstract:
Transforming growth factor-β (TGF-β) belongs to a group of biologically active cytokines that bind to its receptors to activate Smad signaling and non-Smad signaling pathways. The biological functions of TGF-β include promoting cell epithelial-mesenchymal transition, tissue fibrosis, angiogenesis and tumor immune evasion, as well as dual effects of cancer suppression and cancer promotion. Given the fact that the ligand- and receptors-mediated abnormal activation of TGF-β signaling pathways play an important role in the pathogenesis of multiple diseases such as malignant tumors and tissue fibrosis, more than a dozen small-molecule inhibitors have been developed to block the TGF-β signaling pathways, providing a novel method for controlling the development of these diseases. At present, pirfenidone, an inhibitor for TGF-β production, has been approved for treatment of idiopathic pulmonary fibrosis, while the inhibitors of TGFβRI/ALK5 for therapeutics of tumors or myelodysplastic syndromes, including LY2157299, EW-7197 and LY3200882, are in the phase I to III clinical trials, with additional ones inhibiting TGFβRs such as SB-431542, LY2109761, TP-0427736, and IN-1130 being in the preclinical phase. This paper reviews recent advances in research of small-molecule inhibitors targeting TGF-β and its receptors.
