Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties
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- 作者：Olaf Kinzel ; Laura Llauger-Bufi ; Giovanna Pescatore ; Michael Rowley ; Carsten Schultz-Fademrecht ; Edith Monteagudo ; Massimiliano Fonsi ; Odalys Gonzalez Paz ; Fabrizio Fiore ; Christian Steinkhler ; Philip
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：June 11, 2009
- 年：2009
- 卷：52
- 期：11
- 页码：3453-3456
- 全文大小：134K
- 年卷期：v.52,no.11(June 11, 2009)
- ISSN：1520-4804
文摘
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.