| Bioactivity | MK-0812 is a potent and selective CCR2 antagonist with low nM affinity for CCR2. | ||||||||||||
| Invitro | 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-Ly6Chi 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 Ly6Chi monocytes and a corresponding elevation in the CCR2 ligand CCL2[2]. | ||||||||||||
| Name | MK-0812 | ||||||||||||
| CAS | 624733-88-6 | ||||||||||||
| Formula | C24H34F3N3O3 | ||||||||||||
| Molar Mass | 469.54 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Wisniewski T, et al. Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist.J Immunol Methods. 2010 Jan 31;352(1-2):101-10. [2]. Min SH, et al. Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis.Biochem Biophys Res Commun. 2010 Jan 1;391(1):1080-6. |