Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties

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 t...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2009-06, Vol.52 (11), p.3453-3456
Hauptverfasser:	Kinzel, Olaf, Llauger-Bufi, Laura, Pescatore, Giovanna, Rowley, Michael, Schultz-Fademrecht, Carsten, Monteagudo, Edith, Fonsi, Massimiliano, Gonzalez Paz, Odalys, Fiore, Fabrizio, Steinkühler, Christian, Jones, Philip
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacokinetics Biological and medical sciences Cell Line, Tumor Dogs Drug Screening Assays, Antitumor Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacokinetics General aspects HeLa Cells Histone Deacetylase Inhibitors Humans Medical sciences Mice Pharmacology. Drug treatments Quinolines - chemical synthesis Quinolines - pharmacokinetics Rats
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm9004303