CC-90005 is a potent, selective, and orally active inhibitor of protein kinase C-θ (PKC-θ) with an IC50 of 8 nM, demonstrating strong selectivity over PKC-δ (IC50=4440 nM). Additionally, CC-90005 can inhibit T cell activation by IL-2 expression[1].

PKCθ:8 nM (IC50)

CC-90005 exhibits high selectivity with IC50 values for all other family members exceeding 3 μM. It is a moderate inhibitor of CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes. CC-90005 inhibits IL-2 expression in LRS_WBC human PBMCs with an IC50 of 0.15 μM. Additionally, CC-90005 (1-10 μM; 24 h) inhibits T cell proliferation in PBMCs by 51% at 1 μM and 88% at 3 μM[1].

CC-90005 (3-30 mg/kg; p.o. twice daily for 4 days) significantly reduces the popliteal lymph node (PLN) size in a model of chronic T cell activation[1]. Additionally, CC-90005 (100 mg/kg; a single p.o.) significantly inhibits plasma and spleen IL-2 release by 51% and 54%, respectively[1]. CC-90005 demonstrates reasonable oral bioavailability (66% in rats and 46% in dogs) and Cmax (1.18 μM in rats and 1.2 μM in dogs) following oral administration (10 mg/kg in rats and 3 mg/kg in dogs)[1]. Following intravenous administration (2 mg/kg in rats and 1 mg/kg in dogs), CC-90005 exhibits a mean residence time of 0.52 h in rats and 2.0 h in dogs, clearance (CL) of 69.1 mL/min/kg in rats and 20.5 mL/min/kg in dogs, and volume of distribution at steady state (Vss) of 2.11 L/kg in rats and 2.44 L/kg in dogs[1].