Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties
Journal of Medicinal Chemistry2009Vol. 52(11), pp. 3453–3456
Citations Over TimeTop 17% of 2009 papers
Olaf Kinzel, Laura Llauger-Bufi, Giovanna Pescatore, Michael Rowley, Carsten Schultz‐Fademrecht, Edith Monteagudo, Massimiliano Fonsi, Odalys Gonzalez Paz, Fabrizio Fiore, Christian Steinkühler, Philip Jones
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.
Related Papers
- → A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity(2013)65 cited
- → The histone deacetylase inhibitor vorinostat induces calreticulin exposure in childhood brain tumour cells in vitro(2010)28 cited
- Antitumor Effects of the Histone Deacetylase Inhibitor Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Human Retinoblastoma Cell Lines: Therapeutic Implications(2008)
- Progress in clinical trial of histone deacetylase (HDAC) inhibitors for non-small cell lung cancers*(2014)
- → Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model(2016)