Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 19, Issue 12, Pages 3678-3689Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.01.063
Keywords
Histone acetyltransferase; PCAF; Database screening; Epigenetics; Pyridoisothiazolones
Funding
- Wilhelm Sander Foundation
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We present a combination of database screening, synthesis and in vitro testing to identify novel histone acetyltransferase (HAT) inhibitors. The National Cancer Institute compound collection (NCI) and several commercial databases were filtered by similarity-based virtual screening to find new HAT inhibitors. Employing the recombinant HAT p300/CBP-associated factor (PCAF) and two different histone substrates for screening, pyridoisothiazolones were identified as inhibitors of human PCAF. Due to the limited solubility of the initial hits, we synthesized and tested them on PCAF. The compounds inhibit the proliferation of cancer cells. In summary, valuable chemical tools and potential lead candidates for new anticancer agents directed against HATs as new targets have been identified. (C) 2011 Elsevier Ltd. All rights reserved.
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