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

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.

SUBMITTER: Xu G

PROVIDER: S-EPMC6022239 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Xu Guangwei G Wang Tianqi T Li Yongtao Y Huang Zhi Z Wang Xin X Zheng Jianyu J Yang Shengyong S Fan Yan Y Xiang Rong R

Journal of enzyme inhibition and medicinal chemistry 20181201 1

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 ex ...[more]

PMID: 29932010

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