In vitro, Aplaviroc exerts potent activity against HIV-1 strains. And the three strains are wild-type R5 HIV-1 strains (HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW) with IC50 values of 0.1 to 0.4 nM. What’s more, Aplaviroc is substantially more potent than previous inhibitors. The published CCR5 inhibitors are E921/TAK-779 and AK671/SCH-C.
Besides, Aplaviroc suppresses the infectivity and replication of two HIV-1MDR variants. It inhibits HIV-1MM and HIV-1JSL, at extremely low concentrations (IC50 values of 0.4 to 0.6 nM).
Furthermore, Aplaviroc binds to CCR5 with high affinity. The Kd values thus determined for Aplaviroc, E913, E921/TAK-779, and AK671/SCH-C are 2.9±1.0, 111.7±3.5, 32.2±9.6, and 16.0±1.5 nM, respectively. Furthermore, Aplaviroc potently blocks rgp120/sCD4 binding to CCR5. And the IC50 value is 2.7 nM. These results suggest the potent activity of Aplaviroc.
Add this compound against R5 HIV-1 stems from its binding to ECL2B and/or its vicinity with high affinity. As a result, it leads to the inhibition of gp120/CD4 binding to CCR5.
In vivo, The concentration of Aplaviroc reaches the maximal concentration immediately after intraperitoneal administration. and the concentration of Aplaviroc also decreases rapidly.
in a hu-PBMC-NOG mouse. Aplaviroc (AK602, 60 mg/kg, bid, daily) suppresses R5 HIV-1 viremia after a single intraperitoneal administration, bid, daily.
And the numbers of CD4+ cells/μL in saline-treated mice are significantly less than AK602-treated.
In conclusion, Aplaviroc is a CCR5 antagonist. And it has the potential for HIV research.