CPTH2 is an inhibitor of HAT activity of Gcn5.
Histone acetyltransferases (HATs) has been identified to add the acetyl group on the specific lysine of histone H3 and H4 N-termini, and such signatures are able to increase the accessibility of the underlying chromatin at specific genes or over vast regions of the genome. Gcn5p is a chimeric protein made up of a number of functional domains.
In vitro: Previous study identified a novel molecule named CPTH2, which was selected based on its inhibitory effect on the growth of a gcn5Delta strain. This study indicated a specific chemical-genetic interaction between CPTH2 and HAT Gcn5p, suggesting that CPTH2 could inhibit the dependent functional network of Gcn5p. In addition, CPTH2 was found to be able to inhibit an in-vitro HAT reaction, which could be reverted by increasing concentration of histone H3 [1].
In vivo: In vivo, CPTH2 could decrease the acetylation of bulk histone H3 at the specific H3-AcK14 site [1].
Clinical trial: Up to now, CPTH2 is still in the preclinical development stage.
Reference:
[1] F. Chimenti, B. Bizzarri, E. Maccioni, et al. A novel histone acetyltransferase inhibitor modulating Gcn5 network: Cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone. Journal of Medicinal Chemistry 52, 530-536 (2009).