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