Field-based rational design of p300 histone acetyltransferase inhibitor and systematic evaluation as an anti-fibrotic agent.
Soo-Yeon HwangSoo-Yeon ParkJung Yeon HongSoo Yeon LeeJae-Ho ShinYounghwa NaMyung Hyun SohnHo-Geun YoonYoungjoo KwonPublished in: Chemical communications (Cambridge, England) (2021)
(E)-3-(3-(4-((3-Carbamoylbenzyl)oxy)-3-iodo-5-methoxyphenyl) acryloyl)benzamide (A6) was found to be a potent p300 inhibitor (IC50 = 870 nM) showing a similar binding mode to that of acetyl-CoA, a p300 substrate, and effective anti-fibrotic activity in both TGF-β1-stimulated lung fibroblast cells and bleomycin-induced in vivo lung fibrosis mice.
Keyphrases
- induced apoptosis
- systemic sclerosis
- idiopathic pulmonary fibrosis
- cell cycle arrest
- diabetic rats
- high glucose
- dna methylation
- transforming growth factor
- photodynamic therapy
- oxidative stress
- high fat diet induced
- signaling pathway
- pulmonary fibrosis
- type diabetes
- anti inflammatory
- metabolic syndrome
- transcription factor
- pi k akt
- epithelial mesenchymal transition
- skeletal muscle
- amino acid
- wild type
- wound healing