C-646

A reversible, cell-permeable pyrazolone p300/CBP HAT inhibitor (Ki = 400 nM), which competes with acetyl-CoA for the p300 Lys-CoA binding pocket. Demonstrates 86% inhibition against p300 at 10 nM. Less than 10% inhibition against serotonin N-acetyltransferase, PCAF, GCN5, Rtt109, Sas, and MOZ HATs in a chemical screening assay. Treatment of C3H 10T1/2 mouse fibroblasts at 25 uM results in an inhibitory effect against basal and TSA-inducible acetylation of histones H3 and H4. Shown to inhibit human cell growth in melanoma and non-small cell-lung cancer cell lines at 10 uM with similar or higher potency than peptide-based bisubstrate p300/CBP HAT inhibitor Lys-CoA-Tat at 25 uM.