Aplaviroc hydrochloride

Research use only, not for human use.

Aplaviroc (GSK-873140;GW 873140;AK-602;ONO-4128) is a potent, noncompetitive, allosteric antagonist of the CCR5 receptor.

Aplaviroc (GSK-873140;GW 873140;AK-602;ONO-4128) is a potent, noncompetitive, allosteric antagonist of the CCR5 receptor with pKb of 8.6; blocks the calcium response effects of CCR5 activation by CCL5, and potently blocks in vitro the infection of R5-tropic HIV-1 (R5-HIV-1) at subnanomolar IC50.HIV Infection Phase 3 Discontinued.

Aplaviroc exerts potent activity against three wild-type R5 HIV-1 strains (HIV-1Ba-L, HIV-1JRFL and HIV-1MOKW) 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-1MDR variants, HIV-1MM and HIV-1JSL, at extremely low concentrations (IC50 values of 0.4 to 0.6 nM). 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. 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.

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. 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.

AK-602 | GW 873140 | ONO-4128 | GSK-873140

GPCR/G Protein

Chemokine Receptor

Chemokine Receptor

Infection

HIV Infection

461023-63-2

614.18

C33H44ClN3O6

>98% (HPLC)

In Vitro:?DMSO : 200 mg/mL (325.64 mM)

CCCCN1C(=O)C(NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)C(C5CCCCC5)O.Cl

4-[4-[[(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid hydrochloride

(-20℃)

With Ice Pack

≥ 2 years