Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including C-C chemokine ligand type 2 (CCL2) and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation[3]. Cenicriviroc (CVC; also known as TAK-652 and TBR-652) is an orally active, dual CCR2/CCR5 antagonist with IC50 values of 5.9 nM and 0.29 nM in clinical isolates. During the 10-day CVC treatment period, CVC showed a potent dose-response effect on HIV-1 RNA levels which persisted well after discontinuation of treatment. The mean HIV-1 RNA reductions remained significant through day 15 for all CVC dose groups. Those dates suggested CVC to be a potent, well-tolerated anti-HIV drug with potential for additional benefit through a CCR2-mediated anti-inflammatory effect[4]. In the TG-induced model of peritonitis, CVC treatment led to dose-related decreases in monocyte/macrophage recruitment, of similar or greater magnitude than those observed with dexamethasone (positive control), and achieving statistical significance at doses ≥20 mg/kg/day (p < 0.05). In the NASH model, plasma ALT (alanine aminotransferase) levels were significantly decreased with both CVC doses (20 mg/kg/day; 100 mg/kg/day) versus vehicle control (p < 0.05)[3].
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