Background:

Teijin compound 1 is a specific CCR 2 antagonist with IC50s of 24 and 180 nM in chemotaxis and binding assay, respectively.

Ile263 and Thr292 in CCR2 contribute significantly to binding of Teijin compound 1 in CCR2. Residue Glu291 in TM7, a highly conserved residue in many CC chemokine receptors, contributes substantially to binding of the protonated Teijin compound 1, and CCL2. His121 on TM3 and Ile263 on TM6 also strongly interact with Teijin compound 1[2].

In ApoE-deficient mice, Vp-TSL targets specifically aortic plaque endothelial VCAM-1 and Teijin compound 1 reduces the mouse monocyte/macrophage cell line (RAW 264.7) adhesion/ infiltration into the aorta[3].

参考文献:
[1]. Moree WJ, et al. Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series. Bioorg Med Chem Lett. 2008 Mar 15;18(6):1869-73.
[2]. Hall SE, et al. Elucidation of binding sites of dual antagonists in the human chemokine receptors CCR2 and CCR5. Mol Pharmacol. 2009 Jun;75(6):1325-36.
[3]. Calin M, et al. VCAM-1 directed target-sensitive liposomes carrying CCR2 antagonists bind to activated endothelium and reduce adhesion and transmigration of monocytes. Eur J Pharm Biopharm. 2015 Jan;89:18-29.