Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties.
Article Details
- CitationCopy to clipboard
Kinzel O, Llauger-Bufi L, Pescatore G, Rowley M, Schultz-Fademrecht C, Monteagudo E, Fonsi M, Gonzalez Paz O, Fiore F, Steinkuhler C, Jones P
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.
- PubMed ID
- 19441846 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Vorinostat Histone deacetylase 1 IC 50 (nM) 30 N/A N/A Details Vorinostat Histone deacetylase 2 IC 50 (nM) 82 N/A N/A Details Vorinostat Histone deacetylase 3 IC 50 (nM) 57 N/A N/A Details Vorinostat Histone deacetylase 6 IC 50 (nM) 43 N/A N/A Details