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
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.