Epacadostat (INCB024360)

Epacadostat (INCB024360) is an orally available hydroxyamidine and inhibitor of indoleamine 2,3- dioxygenase (IDO1). It shows little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). Epacadostat displays potential immunomodulating and antineoplastic activities. L-tryptophan (L-Trp) is an essential amino acid necessary for protein synthesis in mammalian cells and the L-Trp to kynurenine (Kyn) pathway is firmly established as a key regulator of innate and adaptive immunity. Catabolism of L-Trp to Kyn maintains an immunosuppressive microenvironment by starving immune cells of L-Trp and releasing degradation products of L-Trp that have immunosuppressive functions. Indoleamine 2,3-dioxygenases (IDO1 and IDO2) and Tryptophan 2,3 dioxygenase (TDO) are upregulated in many tumors, providing cancer cells with an avenue for immune evasion. Epacadostat, also known as INCB024360, is a IDO1 selective inhibitor that has been shown to increase NK and T-cell activity, and result in tumor reduction in clinical trials.