Property-based optimization of hydroxamate-based γ-lactam HDAC inhibitors to improve their metabolic stability and pharmacokinetic profiles

Cited 24 time in scopus
Metadata Downloads
Title
Property-based optimization of hydroxamate-based γ-lactam HDAC inhibitors to improve their metabolic stability and pharmacokinetic profiles
Author(s)
E Choi; C H Lee; M Cho; J J Seo; J S Yang; Soo Jin Oh; K Lee; S K Park; H M Kim; H J Kwon; G Han
Bibliographic Citation
Journal of Medicinal Chemistry, vol. 55, no. 23, pp. 10766-10770
Publication Year
2012
Abstract
Hydroxamate-based HDAC inhibitors have promising anticancer activities but metabolic instability and poor pharmacokinetics leading to poor in vivo results. QSAR and PK studies of HDAC inhibitors showed that a γ-lactam core and a modified cap group, including halo, alkyl, and alkoxy groups with various carbon chain linkers, improved HDAC inhibition and metabolic stability. The biological properties of the γ-lactam HDAC inhibitors were evaluated; the compound designated 8f had potent anticancer activity and high oral bioavailability.
ISSN
0022-2623
Publisher
Amer Chem Soc
DOI
http://dx.doi.org/10.1021/jm3009376
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.