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Inhibition of the PCAF histone acetyl transferase and cell proliferation by isothiazolones

Dekker, F. J., Ghizzoni, M., van der Meer, N., Wisastra, R. & Haisma, H. J., 15-Jan-2009, In : Bioorganic & Medicinal Chemistry. 17, 2, p. 460-466 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyl transferases (HATs) in the cell and have relevance for oncology. We present a systematic investigation of the inhibition of the HAT p300/CBP Associated Factor (PCAF) by isothiazolones with different substitutions. 5-chloroisothiazolones proved to be the most potent inhibitors of PCAF. The growth inhibition of 4 different cell lines was studied and the growth of two cell lines (A2780 and HEK 293) was inhibited at micromolar concentrations by 5-chloroisothiazolones. Furthermore, the 5-chloroisothiazolone preservative Kathon (TM) CG that is used in cosmetics inhibited PCAF and the growth of cell lines A2780 and HEK 293, which indicates that this preservative should be applied with care. (C) 2008 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)460-466
Number of pages7
JournalBioorganic & Medicinal Chemistry
Volume17
Issue number2
Publication statusPublished - 15-Jan-2009

    Keywords

  • PCAF, Histone acetyl transferase, Acetylation, Isothiazolones, LYSINE ACETYLTRANSFERASES, CHROMATIN TRANSCRIPTION, MODIFYING ENZYMES, CRYSTAL-STRUCTURE, P300, MECHANISM, GCN5, COACTIVATORS, SUPERFAMILY, PROGRESSION

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