Ancriviroc

Ancriviroc (SCH-351125) is an orally active CCR5 antagonist with an IC₅₀ value of 13 nM against hCCR5. Ancriviroc specifically binds to hCCR5, blocks ligand-induced signal transduction, calcium influx, GTPγS binding, chemotaxis, ligand binding, and HIV-1 entry, induces conformational changes in CCR5, and inhibits infection and replication of R5-tropic HIV-1^[1][2]. In Vitro:Ancriviroc (0.3-10 nM; 1 h) potently inhibits the binding of RANTES to CCR5 expressed on the membrane of CHO cells, with a K_i value of 2.9 nM^[1].
Unlabeled Ancriviroc (10 μM, 2 h) binds to CCR5 on B550 cells with high affinity, with a K_d value of 9.27 nM and a B_max value of 1.98 × 10^-4 fmol/cell^[1].
Ancriviroc inhibits agonist-induced CCR5 activation in CHO-CCR5 cell membranes, with an IC₅₀ of approximately 16 nM for MIP-1β-induced [³⁵S]GTPγS binding^[1].
Ancriviroc (1 h) inhibits the entry of R5 envelope-pseudotyped HIV-1 into U87-CD4-CCR5 cells, with a mean IC₅₀ of 0.69 nM^[1].
Ancriviroc (SCH-351125) (at concentrations up to 10000 nM for 3 h) potently inhibits the binding of [¹²⁵I]-CCL3 to membranes of B300-19 cells expressing human CCR5, with an IC₅₀ of 13 nM; it shows no activity against mouse CCR5 even at concentrations as high as 10000 nM^[2].
Ancriviroc (administered 1 min prior to CCL3) inhibits CCL3-induced intracellular Ca²⁺ elevation in CCR5-expressing B300-19 cells, with an IC₅₀ of 81 nM; it shows no activity against mouse CCR5 even at concentrations as high as 10000 nM^[2]. In Vivo:Ancriviroc (SCH-C) (3-30 mg/kg per day; p.o.; twice daily; for 28 consecutive days) exhibits potent, dose-dependent antiviral activity in SCID-hu Thy/Liv mice, with the 30 mg/kg per day dose reducing p24 levels to the lower limit of detection and decreasing viral RNA copy number by 3.6 log₁₀^[1].
Ancriviroc (0.01-10 mg/kg; p.o.; single administration) dose-dependently occupies CCR5 receptors in CCR5 transgenic mice, with an ED₅₀ of 0.10 mg/kg, and achieves nearly complete receptor occupancy at doses of 1 mg/kg and 10 mg/kg^[2].