The recognition of viral single‐stranded RNA by Toll‐like receptor 7 (TLR7) had been shown to induce an antiviral response in the host against hepatitis C virus (HCV). PF-4878691 is a potent and selective TLR7 agonist. It activated nuclear factor-κB in HEK293 cells transfected with TLR7 at a concentration of >3.3μmol/L. PF-4878691 induced the production of interferon (IFN)-α from human peripheral blood mononuclear cells (PBMCs) at a concentration of 0.041μmol/L. The stimulation of PBMCs with PF-4878691 also led to the activation of natural killer cells[1]. The supernatants from PBMCs stimulated with 0.1μM PF-4878691 inhibited the proliferation of tumor cell lines Hs294T and 769-P. PF-4878691 at low nanomolar concentrations (≥0.04μM) stimulated the production of IFN-inducible protein-10, interleukin (IL)-1 receptor antagonist, monocyte chemotactic protein-1, and tumor necrosis factor-related apoptosis-inducing ligand from human PBMCs. PF-4878691 at 3–30μM also induced the production of IL-12p70, IL-18, and IFN-γ. In a B16 melanoma mouse model, six oral doses of PF-4878691 (150mg/kg, every other day) significantly delayed the onset of lung colonies[2].
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