2. Academic Validation
  3. Design, synthesis and biological evaluation of exiguamine A analogues as IDO1 inhibitors

Design, synthesis and biological evaluation of exiguamine A analogues as IDO1 inhibitors

  • Eur J Med Chem. 2021 Nov 5:223:113631. doi: 10.1016/j.ejmech.2021.113631.
Junmin Dong 1,  Xuan Pan 1,  Ying Yang 1,  Guangyan Zhang 1,  Zhiyan Xiao 1,  Zhanzhu Liu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, PR China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, PR China. Electronic address: liuzhanzhu@imm.ac.cn.
PMID: 34147748 DOI: 10.1016/j.ejmech.2021.113631
Abstract

A series of exiguamine A analogues were designed and synthesized via 15 steps. Their inhibitory activities against IDO1 were tested and the structure-activity relationships were studied. Most compounds exhibited potent IDO1 inhibitory activities with IC50 values at the level of 10-7-10-8 M. Compound 21f was the most potent IDO1 Inhibitor with an IC50 value of 65.3 nM, which was comparable with the positive control drug epacadostat (IC50 = 46 nM). Moreover, compound 21f showed higher selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO) and no cytotoxicity at its effective concentration, rending it justifiable for further optimization and evaluation.

Keywords

Cancer immunotherapy; Exiguamine A; Indoleamine 2,3-dioxygenase 1.

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