Aplaviroc (hydrochloride)

Aplaviroc (AK 602) hydrochloride, a SDP derivative, is a CCR5 antagonist, with IC₅₀s of 0.1-0.4 nM for HIV-1_Ba-L, HIV-1_JRFL and HIV-1_MOKW. IC50 & Target: IC50: 0.1-0.4 nM (HIV-1_Ba-L, HIV-1_JRFL, HIV-1_MOKW)^[1]. 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 IC₅₀ 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 (IC₅₀ 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 IC₅₀ 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^[1]. In Vivo: The concentration of Aplaviroc (AK602) reached the maximal concentration immediately after intraperitoneal administration and decreased rapidly^[2].
Aplaviroc (AK602, 60 mg/kg, bid, daily) suppresses R5 HIV-1 viremia in hu-PBMC-NOG mice^[2].