In vitro activity: Cenicriviroc (formerly known as TAK-652 or TBR-652) is a novel, orally bioactive, and dual antagonist of CCR2/CCR5, it also inhibits both HIV-1 and HIV-2, and has the potential for the treatment of HIV infection. TAK-652 inhibited the binding of RANTES (regulated on activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta to CCR5-expressing cells at nanomolar concentrations. TAK-652 could also suppress the binding of monocyte chemotactic protein 1 (MCP-1) to CCR2b-expressing cells. However, its inhibitory effect on ligand binding to other chemokine receptors was limited. TAK-652 was active against CCR5-using (R5) HIV-1 but totally inactive against CXCR4-using (X4) HIV-1.

Kinase Assay: Cenicriviroc prevents human immunodeficiency virus type 1 (HIV-1) from cellular entry with effective concentration 50% EC50 of 0.03, 0.33, 0.45 and 0.98 nM for the 4 R5 HIV-2 clinical isolates tested. 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.

Cell Assay: AK-652 inhibited the binding of RANTES (regulated on activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta to CCR5-expressing cells at nanomolar concentrations. TAK-652 could also suppress the binding of monocyte chemotactic protein 1 (MCP-1) to CCR2b-expressing cells.