For research use only. Not for therapeutic Use.
MK-0812 is a potent and selective CCR2 antagonist with low nM affinity for CCR2.
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].
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].
| Catalog Number | I004357 |
| CAS Number | 624733-88-6 |
| Synonyms | [(1S,3R)-3-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone |
| Molecular Formula | C24H34F3N3O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C24H34F3N3O3/c1-15(2)23(7-4-18(11-23)29-20-6-9-33-14-21(20)32-3)22(31)30-8-5-19-16(13-30)10-17(12-28-19)24(25,26)27/h10,12,15,18,20-21,29H,4-9,11,13-14H2,1-3H3/t18-,20+,21-,23+/m1/s1 |
| InChIKey | MTMDXAIUENDNDL-RJSMDTJLSA-N |
| SMILES | CC(C)C1(CCC(C1)NC2CCOCC2OC)C(=O)N3CCC4=C(C3)C=C(C=N4)C(F)(F)F |
| 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. |
