MK-0812 is a potent and selectiveCCR2antagonist with low nM affinity forCCR2.

MK-0812 completely blocks all MCP-1 mediated response in a concentration dependent manner, with an IC₅₀of 3.2 nM. This value is similar to the potency observed for the inhibition of¹²⁵I-MCP-1 binding by MK-0812 on isolated monocytes (IC₅₀4.5 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 IC₅₀for MK-0812 in whole blood assays is 8 nM^[1]MK0812 is a potent and selective small molecule CCR2 antagonist^[2].

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^himonocytes 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^himonocytes and a corresponding elevation in the CCR2 ligand CCL2^[2].

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Solid

C₂₄H₃₄F₃N₃O₃

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