MK-0812

MK-0812 is a potent and selective CCR2 antagonist with low nM affinity for CCR2. IC50 & Target: CCR2^[1] In Vitro: MK-0812 completely blocks all MCP-1 mediated response in a concentration dependent manner, with an IC₅₀ of 3.2 nM. This value is similar to the potency observed for the inhibition of ¹²⁵I-MCP-1 binding by MK-0812 on isolated monocytes (IC₅₀ 4.5 nM). In fact, the antagonist not only completely blocks the shape change response to exogenous MCP-1, but also results in a monocyte forward scatter measurement below unstimulated or basal levels. The addition of MK-0812 to rhesus blood also inhibits MCP-1 induced monocyte shape change. The IC₅₀ for MK-0812 in whole blood assays is 8 nM^[1] MK0812 is a potent and selective small molecule CCR2 antagonist^[2]. In Vivo: MK-0812 is administered by continuous i.v. infusion to maintain a constant level of the drug in blood^[1]. Administration of MK0812 at 30 mg/kg, p.o. reduces the frequency of Ly6G^-Ly6C^hi monocytes in the peripheral blood, while no impact on circulating Ly6G⁺Ly6C⁺ neutrophil frequency is observed. In addition, MK0812 treatment causes a dose-dependent reduction in circulating Ly6C^hi monocytes and a corresponding elevation in the CCR2 ligand CCL2^[2].