2. Academic Validation
  3. Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum

Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum

  • J Med Chem. 2009 Apr 23;52(8):2185-7. doi: 10.1021/jm801654y.
Vishal Patel 1,  Ralph Mazitschek,  Bradley Coleman,  Cokey Nguyen,  Sameer Urgaonkar,  Joseph Cortese,  Robert H Barker,  Edward Greenberg,  Weiping Tang,  James E Bradner,  Stuart L Schreiber,  Manoj T Duraisingh,  Dyann F Wirth,  Jon Clardy
Affiliations

Affiliation

  • 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
PMID: 19317450 DOI: 10.1021/jm801654y
Abstract

A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.

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