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

Eunhyun Choi, Chulho Lee, Misun Cho, Jeong Jea Seo, Jee Sun Yang, Soo Jin Oh, Kiho Lee, Song Kyu Park, Hwan Mook Kim, Ho Jeong Kwon, Gyoonhee Han

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23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)10766-10770
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number23
Publication statusPublished - 2012 Dec 13


All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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