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ID: ALA4359827

Journal: ACS Med Chem Lett

Title: Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors.

Authors: Tu W, Yang F, Xu G, Chi J, Liu Z, Peng W, Hu B, Zhang L, Wan H, Yu N, Jin F, Hu Q, Zhang L, He F, Tao W.

Abstract: A novel series of imidazoisoindoles were identified as potent indoleamine-2,3-dioxygenase (IDO) inhibitors. Lead optimization toward improving potency and eliminating CYP inhibition resulted in the discovery of lead compound 25, a highly potent IDO inhibitor with favorable pharmacokinetic properties. In the MC38 xenograft model in hPD-1 transgenic mice, 25 in combination with the anti-PD-1 monoclonal antibody (SHR-1210) achieved a synergistic antitumor effect superior to each single agent.

CiteXplore: 31223453

DOI: 10.1021/acsmedchemlett.9b00114