2. Academic Validation
  3. Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties

Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties

  • J Med Chem. 2009 Jun 11;52(11):3453-6. doi: 10.1021/jm9004303.
Olaf Kinzel 1,  Laura Llauger-Bufi,  Giovanna Pescatore,  Michael Rowley,  Carsten Schultz-Fademrecht,  Edith Monteagudo,  Massimiliano Fonsi,  Odalys Gonzalez Paz,  Fabrizio Fiore,  Christian Steinkühler,  Philip Jones
Affiliations

Affiliation

  • 1 IRBM/Merck Research Laboratories, Pomezia, Italy. olaf_kinzel@merck.com
PMID: 19441846 DOI: 10.1021/jm9004303
Abstract

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.

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