Cenicriviroc is an orally active, dual antagonist of CCR2/CCR5. It also inhibits both HIV-1 and HIV-2, and displays potent anti-infective and anti-inflammatory activity.
Cenicriviroc prevents HIV-1 from cellular entry . Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc are 0.03, 0.33, 0.45 and 0.98 nM. The dual-tropic and the X4-tropic HIV-2 strains are resistant to cenicriviroc with EC50 at >1000 nM, and MPI at 33% and 4%, respectively .
Cenicriviroc (≥20 mg/kg/day) significantly reduces monocyte/macrophage recruitment in vivo. In the NASH model, cenicriviroc significantly reduces the non-alcoholic fatty liver disease activity score. Cenicriviroc treatment has no notable effect on body or liver/kidney weight .
Male C57BL/6 mice (n=44; 8-10 weeks of age) are allocated to receive treatments via oral gavage (PO) on Days 1-5 in the following groups: non-disease control, vehicle control twice daily (BID), Cenicriviroc 5 mg/kg/day (Cenicriviroc5) BID, Cenicriviroc 20 mg/kg/day (Cenicriviroc20) BID, Cenicriviroc 100 mg/kg/day (Cenicriviroc100) BID, Cenicriviroc20 QD, and positive control (corticosteroid known to reduce inflammation in a variety of animal models) 1 mg/kg QD. On Day 4, peritonitis is induced via IP injection of TG 3.85% (1 mL/animal) 2 hours post-dose in all groups except non-disease controls .