Aplaviroc (AK 602) hydrochloride, a SDP derivative, is a CCR5 antagonist, with IC 50 s of 0.1-0.4 nM for HIV-1 Ba-L , HIV-1 JRFL and HIV-1 MOKW .
In Vitro
Aplaviroc exerts potent activity against three wild-type R5 HIV-1 strains (HIV-1 Ba-L , HIV-1 JRFL and HIV-1 MOKW ) with IC 50 values of 0.1 to 0.4 nM. Aplaviroc is substantially more potent than two previously published CCR5 inhibitors, E921/TAK-779 and AK671/SCH-C. Aplaviroc suppresses the infectivity and replication of two HIV-1 MDR variants, HIV-1 MM and HIV-1 JSL , at extremely low concentrations (IC 50 values of 0.4 to 0.6 nM). Aplaviroc binds to CCR5 with high affinity. The K d 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. Aplaviroc potently blocks rgp120/sCD4 binding to CCR5 with an IC 50 value of 2.7 nM. These results suggest that the potent activity of Aplaviroc against R5 HIV-1 stems from its binding to ECL2B and/or its vicinity with high affinity, resulting in inhibition of gp120/CD4 binding to CCR5. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
The concentration of Aplaviroc (AK602) reached the maximal concentration immediately after intraperitoneal administration and decreased rapidly. Aplaviroc (AK602, 60 mg/kg, bid, daily) suppresses R5 HIV-1 viremia in hu-PBMC-NOG mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: hu-PBMC-NOG mice. Dosage: 60 mg/kg. Administration: Single intraperitoneal administration, bid, daily. Result: The numbers of CD4 + cells/μL in saline-treated mice were significantly less than those of AK602-treated, ddI-treated, or uninfected mice.
Form:Solid
IC50& Target:HIV-1 Ba-L 0.4 nM (IC 50 ) HIV-1 JRFL 0.1 nM (IC 50 ) HIV-1 MOKW 0.2 nM (IC 50 ) CCR5
