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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10766-10770
Number of pages5
JournalJournal of Medicinal Chemistry
Volume55
Issue number23
DOIs
Publication statusPublished - 2012 Dec 13

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Lactams
Histone Deacetylase Inhibitors
Pharmacokinetics
Quantitative Structure-Activity Relationship
Biological Availability
Carbon

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Choi, Eunhyun ; Lee, Chulho ; Cho, Misun ; Seo, Jeong Jea ; Yang, Jee Sun ; Oh, Soo Jin ; Lee, Kiho ; Park, Song Kyu ; Kim, Hwan Mook ; Kwon, Ho Jeong ; Han, Gyoonhee. / Property-based optimization of hydroxamate-based γ-lactam HDAC inhibitors to improve their metabolic stability and pharmacokinetic profiles. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 23. pp. 10766-10770.
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Property-based optimization of hydroxamate-based γ-lactam HDAC inhibitors to improve their metabolic stability and pharmacokinetic profiles. / Choi, Eunhyun; Lee, Chulho; Cho, Misun; Seo, Jeong Jea; Yang, Jee Sun; Oh, Soo Jin; Lee, Kiho; Park, Song Kyu; Kim, Hwan Mook; Kwon, Ho Jeong; Han, Gyoonhee.

In: Journal of Medicinal Chemistry, Vol. 55, No. 23, 13.12.2012, p. 10766-10770.

Research output: Contribution to journalArticle

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AU - Choi, Eunhyun

AU - Lee, Chulho

AU - Cho, Misun

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AU - Yang, Jee Sun

AU - Oh, Soo Jin

AU - Lee, Kiho

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AU - Han, Gyoonhee

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