Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum

被引：65

作者：

Patel, Vishal ^{[1
,2
]}

Mazitschek, Ralph ^{[1
,3
,4
]}

Coleman, Bradley ^{[2
]}

Nguyen, Cokey ^{[5
]}

Urgaonkar, Sameer ^{[3
,4
]}

Cortese, Joseph ^{[3
,4
]}

Barker, Robert H., Jr. ^{[5
]}

Greenberg, Edward ^{[3
,4
]}

Tang, Weiping ^{[3
,4
]}

Bradner, James E. ^{[3
,4
]}

Schreiber, Stuart L. ^{[3
,4
]}

Duraisingh, Manoj T. ^{[2
]}

Wirth, Dyann F. ^{[2
]}

Clardy, Jon ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[3] MIT, Broad Inst, Cambridge, MA 02139 USA

[4] Harvard Univ, Cambridge, MA 02138 USA

[5] Genzyme Corp, Framingham, MA 01701 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 08期

关键词：

ISOFORM SELECTIVITY; MALARIA; DRUG; RESISTANCE; APICIDIN; HOMOLOG; SIR2;

D O I：

10.1021/jm801654y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2185 / 2187

页数：3

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