Discovery of Novel Class i Histone Deacetylase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities

Yiwu Yao, Zhengchao Tu, Chenzhong Liao, Zhen Wang, Shang Li, Hequan Yao, Zheng Li, Sheng Jiang

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

A successful structure-based design of novel cyclic depsipeptides that selectively target class I HDAC isoforms is described. Compound 11 has an IC50 of 2.78 nM for binding to the HDAC1 protein, and the prodrugs 12 and 13 also exhibit promising antiproliferative activities in the nanomolar range against various cancer cell lines. Compounds 12 and 13 show more than 20-fold selectivity toward human cancer cells over human normal cells in comparison with romidepsin (FK228), demonstrating low probability of toxic side effects. In addition, compound 13 exhibits excellent in vivo anticancer activities in a human prostate carcinoma (Du145) xenograft model with no observed toxicity. Thus, prodrug 13 has therapeutic potential as a new class of anticancer agent for further clinical translation.

Original languageEnglish (US)
Pages (from-to)7672-7680
Number of pages9
JournalJournal of Medicinal Chemistry
Volume58
Issue number19
DOIs
StatePublished - Oct 8 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Discovery of Novel Class i Histone Deacetylase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities'. Together they form a unique fingerprint.

Cite this