781632-38-0Relevant articles and documents
The development of a novel transforming growth factor-β (TGF-β) inhibitor that disrupts ligand-receptor interactions
Wu, Han,Sun, Yu,Wong, Wee Lin,Cui, Jiajia,Li, Jingyang,You, Xuefu,Yap, Lee Fah,Huang, Yu,Hong, Wei,Yang, Xinyi,Paterson, Ian C.,Wang, Hao
, (2020/01/21)
Transforming growth factor-β (TGF-β) plays an important role in regulating epithelial to mesenchymal transition (EMT) and the TGF-β signaling pathway is a potential target for therapeutic intervention in the development of many diseases, such as fibrosis and cancer. Most currently available inhibitors of TGF-β signaling function as TGF-β receptor I (TβR-I) kinase inhibitors, however, such kinase inhibitors often lack specificity. In the present study, we targeted the extracellular protein binding domain of the TGF-β receptor II (TβR-II) to interfere with the protein-protein interactions (PPIs) between TGF-β and its receptors. One compound, CJJ300, inhibited TGF-β signaling by disrupting the formation of the TGF-β-TβR-I-TβR-II signaling complex. Treatment of A549 cells with CJJ300 resulted in the inhibition of downstream signaling events such as the phosphorylation of key factors along the TGF-β pathway and the induction of EMT markers. Concomitant with these effects, CJJ300 significantly inhibited cell migration. The present study describes for the first time a designed molecule that can regulate TGF-β-induced signaling and EMT by interfering with the PPIs required for the formation of the TGF-β signaling complex. Therefore, CJJ300 can be an important lead compound with which to study TGF-β signaling and to design more potent TGF-β signaling antagonists.
HISTONE DEACETYLASE INHIBITORS
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, (2011/04/13)
The disclosure provides compounds of formula I and methods for preparation thereof. The compounds act as inhibitor of histone deacetylase.
