Field-based rational design of p300 histone acetyltransferase inhibitor and systematic evaluation as an anti-fibrotic agent. Issue 68 (23rd July 2020)

• Record Type: Journal Article
• Authors: Hwang, Soo-Yeon; Park, Soo-Yeon; Hong, Jung Yeon; Lee, Soo Yeon; Shin, Jae-Ho; Na, Younghwa; Sohn, Myung Hyun; Yoon, Ho-Geun; Kwon, Youngjoo
• Is Part Of: Chemical communications. Volume 56:Issue 68(2020)
• Page Start: 9795
• Page End: 9798
• Publication Date: 2020-07-23
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc03553j
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Using a field-based design approach, we systematically identified a novel potent p300 inhibitor, A6, with effective anti-fibrotic activity and favorable drug-like properties. Abstract : ( 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.