CP-481715

CP-481715 is a potent, reversible and selective CCR1 antagonist with a K_d of 9.2 nM for human CCR1. CP-481715 is >100-fold selective for CCR1 as compared with a panel of G-protein-coupled receptors including related chemokine receptors. CP-481715 has the potential for rheumatoid arthritis and other inflammatory diseases research^[1]. In Vitro:CP-481715 displaces ¹²⁵I-labeled CCL3 from CCR1-transfected cells with an IC₅₀ of 74 nM^[1].
CP-481715 lacks intrinsic agonist activity but fully blocks the ability of CCL3 and CCL5 to stimulate receptor signaling (Guanosine 5'-O-(thiotriphosphate) incorporation; IC₅₀ = 210 nM), calcium mobilization (IC₅₀ = 71 nM), monocyte chemotaxis (IC₅₀ = 55 nM), and MMP9 release (IC₅₀ = 54 nM)^[1].
CP-481715 retains activity in human whole blood, inhibiting CCL3-induced CD11b up-regulation and actin polymerization (IC₅₀ = 165 and 57 nM, respectively) on monocytes^[1].