382113  Histone Acetyltransferase p300 Inhibitor, C646

4-(4-{[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, HAT p300 Inhibitor, C646

A reversible, cell-permeable pyrazolone p300/CBP HAT inhibitor (K_i = 400 nM), which competes with acetyl-CoA for the p300 Lys-CoA binding pocket. This compound demonstrates 86% inhibition against p300 at 10 nM, but elicits less than 10% inhibition against serotonin N-acetyltransferase, PCAF histone acetyltransferase, GCN5 histone acetyletransferase, Rtt109 histone acetyletransferase, Sas histone acetyl transferase, and MOZ histone acetyltransferase in a chemical screening assay. Treatment of C3H 10T1/2 mouse fibroblasts with 25 µM of compound results in an inhibitory effect against basal and TSA-inducible acetylation of histones H3 and H4. It is also shown to inhibit human cell growth in both melanoma and non-small-cell-lung (NSCL) cancer cell lines at 10 µM with similar or higher potency compared with that of the peptide-based bisubstrate p300/CBP HAT inhibitor Lys-CoA-Tat at 25 µM.