Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties

被引：42

作者：

Kinzel, Olaf ^{[1
]}

Llauger-Bufi, Laura ^{[1
]}

Pescatore, Giovanna ^{[1
]}

Rowley, Michael ^{[1
]}

Schultz-Fademrecht, Carsten ^{[1
]}

Monteagudo, Edith ^{[1
]}

Fonsi, Massimiliano ^{[1
]}

Paz, Odalys Gonzalez ^{[1
]}

Fiore, Fabrizio ^{[1
]}

Steinkuehler, Christian ^{[1
]}

Jones, Philip ^{[1
]}

机构：

[1] Merck Res Labs, IRBM, I-00040 Pomezia, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 11期

关键词：

SERIES; VORINOSTAT; LYMPHOMA; CANCER; AGENT;

D O I：

10.1021/jm9004303

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of a potent, class I selective ketone HDAC inhibitor is shown. It possesses optimized pharmacokinetic properties in preclinical species, has a clean off-target profile, and is negative in a microbial mutagenicity (Ames) test. In a mouse xenograft model it shows efficacy comparable to that of vorinostat at a 10-fold reduced dose.

引用

页码：3453 / 3456

页数：4

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