Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
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- 作者：Vishal Patel ; 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. Dur
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：April 23, 2009
- 年：2009
- 卷：52
- 期：8
- 页码：2185-2187
- 全文大小：79K
- 年卷期：v.52,no.8(April 23, 2009)
- ISSN：1520-4804
文摘
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.