2. Academic Validation
  3. A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma

A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma

  • J Enzyme Inhib Med Chem. 2018 Dec;33(1):1089-1094. doi: 10.1080/14756366.2018.1471688.
Guangwei Xu 1,  Tianqi Wang 1,  Yongtao Li 1,  Zhi Huang 1,  Xin Wang 1,  Jianyu Zheng 2,  Shengyong Yang 3,  Yan Fan 1 4 5,  Rong Xiang 1 4 5
Affiliations

Affiliations

  • 1 a Department of Medicinal Chemistry, School of Medicine , Nankai University , Tianjin , China.
  • 2 b State Key Laboratory and Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering , Nankai University , Tianjin , China.
  • 3 c State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy , Chengdu , China.
  • 4 d State Key Laboratory of Medicinal Chemical Biology , Tianjin , China.
  • 5 e 2011 Project Collaborative Innovation Center for Biotherapy of Ministry of Education, Tianjin , China.
PMID: 29932010 DOI: 10.1080/14756366.2018.1471688
Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) activity links to immune escape of cancers. Inhibition of IDO1 provides a new approach for Cancer treatment. Most clinical IDO1 drugs show marginal efficacy as single agents. On basis of molecular docking and pharmacophore modelling, a novel inhibitor Roxyl-WL was discovered with a half maximal inhibitory concentration (IC50) value of 1 nM against IDO1 and 10-100-fold increased potent activity compared with IDO1 drugs in clinical trials. Roxyl-WL displayed excellent kinase spectrum selectivity with no activity out of the 337 protein kinases. In vitro, Roxyl-WL effectively augmented the proliferation of T cells and reduced the number of regulatory T cell (Tregs).When administered to melanoma (B16F10) tumor-bearing mice orally, Roxyl-WL significantly suppressed tumor growth and induced immune response.

Keywords

IDO1; immunotherapy; inhibitor; melanoma.

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