Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases

Pentadecylidenemalonate 1b, a simplified analogue of anacardic acid, was identified as the first mixed activator/inhibitor of histone acetyltransferases (HATs). It potentiates PCAF HAT activity while inhibiting those of p300/CBP and recombinant CBP. The remarkable apoptotic effect together with the ability to selectively acetylate histone versus non-histone substrates appoint 1b as a lead for the development of anticancer drugs.

Pentadecylidenemalonate 1b is the first histone acetyltransferases (HAT) modulator able to potentiate PCAF (GNAT family) activity while inhibiting that of CBP (p300/CBP family).Figure optionsDownload as PowerPoint slide