Cenicriviroc is an orally bioavailable antagonist of C-C chemokine receptor type 5 (CCR5) and CCR2 that inhibits binding of macrophage inflammatory protein 1α (MIP-1α; IC50 = 2.3 nM) and monocyte chemotactic protein 1 (MCP-1; IC50 = 5.9 nM), respectively, in CHO cells.1 Cenicriviroc is also an antagonist of CCR3 and CCR4 (IC50s = 2.4 and 1.1 μM, respectively), however, it does not inhibit agonist binding to CCR1 or CCR7 at concentrations up to 10 μM. At a concentration of 100 nM, cenicriviroc completely inhibits replication of R5 HIV-1 in U87.CD4.CCR5 cells. Cenicriviroc inhibits replication of the R5 HIV-1 strains JR-FL and KK in peripheral blood mononuclear cells (PBMCs) with EC50 values ranging from 21 to 210 pM and 33 to 91 pM, respectively. In vivo, cenicriviroc (20 mg/kg per day) reduces collagen deposition, levels of collagen type 1 protein and mRNA expression, and non-alcoholic fatty liver disease activity score in a mouse model of non-alcoholic steatohepatitis (NASH).2 It also reduces collagen type 1 protein levels, mRNA expression, and collagen deposition in a mouse model of unilateral ureter obstruction and a rat model of thioacetamide-induced liver fibrosis.
1.Baba, M., Takashima, K., Miyake, H., et al.TAK-652 inhibits CCR5-mediated human immunodeficiency virus type 1 infection in vitro and has favorable pharmacokinetics in humansAntimicrob. Agents Chemother.49(11)4584-4591(2005) 2.Lefebvre, E., Moyle, G., Reshef, R., et al.Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosisPLoS One11(6):e0158156(2016)