CXCR7 modulator 2 is a 7-type C-X-C chemokine receptor (CXCR7) modulator with a Ki of 13 nM.

CXCR7:13 nM (ki)

CXCR7 modulator 2 showed strong CXCR7 binding affinity (Ki = 13 nM) and β-arrestin activity (EC50 = 11 nM). Compared with 11c, CXCR7 modulator 2 also showed improved selectivity in the GPCR panel and showed a higher therapeutic index in the hERG patch clamp assay. CXCR7 modulator 2 exhibited medium to high in vitro turnover in NADPH- supplemented mouse liver microsomes (MLM, 93 μL / min / mg) and hepatocytes (28 μL / min per million cells), which was shown to be more comparable in MDCK Poor passive absorption permeability type II permeability measurement method, and has good water solubility. CXCR7 regulator 2 is rapidly absorbed, with an average maximum plasma concentration (Cmax) of 682 ng / mL, which appears at 0.25 h (Tmax). The corresponding average area under the plasma concentration-time curve (AUC) is 740 ng / mL / h.

The administration of isoproterenol for 9 days induces cardiac fibrosis, evidenced by a fourfold increase in collagen deposition detected by Pixirius red staining relative to the control group. Treatment with CXCR7 modulator 2 significantly reduces cardiac fibrosis, demonstrating its protective effect on CXCR7 modulation in isoproterenol-induced cardiac injury.