The enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in mediating pathological immunosuppression associated with certain diseases, including cancer. Several naphthoquinones inhibit IDO in vitro and in cells, but at low (μM) potency. Importantly, naphthoquinones reduce tumor growth in wild type mice but not in IDO-deficient mice. CAY10581 is a naphthoquinone derivative that potently inhibits IDO (IC50 = 55 nM). It is a more potent inhibitor of IDO than annulin B or 1-methyl-d-tryptophan (1MT). CAY10581 acts as a reversible uncompetitive inhibitor of IDO and demonstrates minimal impact on cell viability at 100 μM after 24 hours.
