Biological Activity of INCB024360

Description:
IC50 Value: 10nM [1]
INCB024360 is a potent IDO1 inhibitor with desirable pharmaceutical properties, which is poised to start clinical trials in cancer patients.
in vitro: In cellular assays,INCB024360 selectively inhibits human IDO1 with IC(50) values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO) [1]. In coculture systems of human allogeneic lymphocytes with dendritic cells (DCs) or tumor cells,INCB024360 inhibition of IDO1 promotes T and natural killer (NK)-cell growth, increases IFN-gamma production, and reduces conversion to regulatory T (T(reg))-like cells. IDO1 induction triggers DC apoptosis, whereas INCB024360 reverses this and increases the number of CD86 (high) DCs, potentially representing a novel mechanism by which IDO1 inhibition activates T cells [1].
in vivo: Consistent with its effects in vitro, administration of INCB024360 to tumor-bearing mice significantly inhibits tumor growth in a lymphocyte-dependent manner [1]. A single dose of INCB023843 orINCB024360 results in efficient and durable suppression of Ido1 activity in the plasma of treated mice and dogs, the former to levels seen in Ido1-deficient mice [2].
Clinical trial: A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy.