Cenicriviroc Mesylate is a dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2 with anti-inflammatory and antiinfective activity.

CCR2:5.9 nM, CCR5:0.29 nM, R5 HIV-1:0.024-0.08 nM (in PBMCs), R5 HIV-2:0.03-0.98 nM (in PBMCs)

Migration of mouse monocytes in response to carbon tetrachloride (CCL2) is reduced following pre-treatment with Cenicriviroc Mesylate (CVC) at 1 μM concentration. Compared to untreated and unstimulated cells, the average fold change in migrating cells is 0.8±0.2 (p>0.05) and 0.7±0.4 (p>0.05) for CCL2-stimulated and unstimulated cells treated with Cenicriviroc Mesylate, respectively [1]. Phenotypic susceptibility testing reveals a median EC50 for Cenicriviroc Mesylate of 0.39 nM for four R5-tropic HIV-2 isolates, whereas dual-tropic and X4-tropic HIV-2 strains are resistant, showing EC50 values >1000 nM with maximum inhibition percentages of 33% and 4%, respectively [2].

Treatment with Cenicriviroc Mesylate results in a dose-dependent reduction in monocyte/macrophage recruitment, reaching statistical significance at dosages of 20 mg/kg/day or higher. When compared to the vehicle-control group, Cenicriviroc Mesylate administration at dosages of 5 mg twice daily (BID), 20 mg BID, 100 mg BID, and 20 mg once daily (QD) leads to decreases in peritoneal lavage monocyte/macrophage counts of 5.7%, 45.2%, 76.5%, and 26.0%, respectively. The effect of Cenicriviroc Mesylate on reducing monocyte/macrophage recruitment is dose-related and demonstrates a correlation with dosage, showing greater efficacy for twice daily (BID) administration compared to once daily (QD). This increased effectiveness is likely due to the higher plasma concentrations achieved with BID dosing and the compound's short half-life of approximately 2 hours in mice [1].