Discovery of Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) and Histone Deacetylase (HDAC) Dual Inhibitors

Kun Fang, Guoqiang Dong, Yu Li, Shipeng He, Ying Wu, Shanchao Wu, Wei Wang, Chunquan Sheng

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


In order to take advantage of both immunotherapeutic and epigenetic antitumor agents, the first generation of dual indoleamine 2,3-dioxygenase 1 (IDO1) and histone deacetylase (HDAC) inhibitors were designed. The highly active dual inhibitor 10 showed excellent and balanced activity against both IDO1 (IC50 = 69.0 nM) and HDAC1 (IC50 = 66.5 nM), whose dual targeting mechanisms were validated in cancer cells. Compound 10 had good pharmacokinetic profiles as an orally active antitumor agent and significantly reduced the l-kynurenine level in plasma. In particular, it showed excellent in vivo antitumor efficacy in the murine LLC tumor model with low toxicity. This proof-of-concept study provided a novel strategy for cancer treatment. Compound 10 represents a promising lead compound for the development of novel antitumor agents and can also be used as a valuable probe to clarify the relationships and mechanisms between cancer immunotherapy and epigenetics.

Original languageEnglish (US)
Pages (from-to)312-317
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number4
StatePublished - Apr 12 2018
Externally publishedYes


  • HDAC
  • IDO1
  • antitumor efficacy
  • cancer immunotherapy
  • dual inhibitors
  • epigenetics

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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