CXCR7 modulator 2

CXCR7 modulator 2 is a modulator of C-X-C Chemokine Receptor Type 7 (CXCR7), with a K_i of 13 nM. IC50 & Target: K_i: 13 nM (CXCR7)^[1]. In Vitro: CXCR7 modulator 2 (compound 18) demonstrates potent CXCR7-binding affinity (K_i=13 nM) and β-arrestin activity (EC₅₀=11 nM). CXCR7 modulator 2 also exhibits improved selectivity in the GPCR panel and an improved therapeutic index in the hERG patch-clamp assay in comparison with 11c. CXCR7 modulator 2 exhibits moderate to high in vitro turn over in both NADPH-supplemented mouse-liver microsomes (MLM, 93 μL/min/mg) and hepatocytes (28 μL/min per million cells), shows poor passive absorptive permeability in the MDCK II-permeability assay, and has good aqueous solubility. CXCR7 modulator 2 is rapidly absorbed with a mean maximal plasma concentration (C_max) of 682 ng/mL, which occurrs at 0.25 h (T_max). The corresponding mean area under the plasma-concentration-versus-time profile (AUC) is 740 ng/mL/h^[1]. In Vivo: The administration of isoproterenol for 9 days leads to the development of cardiac fibrosis, as attested by the approximately 4-fold increase in collagen deposition relative to that in the control, which is detected by picrosirius-red staining. Treatment with CXCR7 modulator 2 results in a statistically significant reduction in cardiac fibrosis, thereby demonstrating the protective role of CXCR7 modulation with CXCR7 modulator 2 in an isoproterenol-induced cardiac injury^[1].