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J Am Chem Soc. 2005 Dec 14;127(49):17182-3.

Synthesis and evaluation of a potent and selective cell-permeable p300 histone acetyltransferase inhibitor.

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  • 1Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.


This paper describes the first potent and selective p300 histone acetyltransferase (HAT) inhibitor which is effective in live cells. This compound 7 is a coenzyme A analogue conjugated to a cell permeabilizing oligoArg peptide via disulfide linkage. This compound was shown to block cellular histone acetylation and transcription using a p300-sensitive reporter. It should thus be broadly useful for dissecting the role of p300 HAT activity in physiologic and disease states.

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