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

J Med Chem

Authors	Vishal Patel Ralph Mazitschek Bradley Coleman Cokey Nguyen Sameer Urgaonkar Joseph Cortese Robert Barker Edward Greenberg Weiping Tang James Bradner Stuart Schreiber Manoj Duraisingh Dyann Wirth Jon Clardy
Keywords	Animals Humans Histone Deacetylases Plasmodium falciparum Acetylation Cell Line, Tumor Structure-Activity Relationship Antimalarials Small Molecule Libraries Histone Deacetylase Inhibitors Recombinant Proteins Kinetics Parasitic Sensitivity Tests
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.
Year of Publication	2009
Journal	J Med Chem
Volume	52
Issue	8
Pages	2185-7
Date Published	2009 Apr 23
ISSN	1520-4804
DOI	10.1021/jm801654y
PubMed ID	19317450
PubMed Central ID	PMC2669731
Links
Grant list	R21 NS053660 / NS / NINDS NIH HHS / United States R21 NS059404 / NS / NINDS NIH HHS / United States R21NS053660 / NS / NINDS NIH HHS / United States R21NS059404 / NS / NINDS NIH HHS / United States

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