for once-a-day dosing

Cerep screens revealed that INCB3284 is a selective CCR2 inhibitor, showing no significant inhibitory activity at a concentration of 1 μM when tested against a panel of >50 ion channels, transporters, chemokine receptors including CCR1, CCR3, CCR5, CXCR3, and CXCR5, and additional GPCRs. In the hERG patch clamp assay, INCB3284 inhibited hERG potassium current with an IC50 of 84 μM. In protein binding, INCB3284 had a high free fraction (58%) in human serum at concentrations of 1 and 10 μM. When incubated with human liver microsomes, INCB3284 exhibited a moderate intrinsic clearance. However, studies with recombinant CYP isozymes showed that INCB003284 is a substrate for CYP3A4 and CYP2D6. When INCB3284 was incubated with human S9 with or without NADPH and the cofactor glutathione, no glutathione adducts were detected. INCB003284 is not a CYP inhibitor, with IC50 values of >25 μM against five major CYP isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. INCB3284 is not a CYP inducer at concentrations up to 10 μM as measured in the luminometric luciferase assay.