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Vesatolimod

CAS No. : 1228585-88-3

MCE 国际站：Vesatolimod

产品活性：Vesatolimod (GS-9620) 是一种有效，选择性，可口服的 Toll 样受体7 (TLR7) 激动剂，EC₅₀ 值为291 nM。

研究领域：Immunology/Inflammation  |  Apoptosis  |  Anti-infection

作用靶点：Toll-like Receptor (TLR)  |  Apoptosis  |  HBV  |  HCV  |  HIV

In Vitro: Vesatolimod (GS-9620) rapidly internalizes into cells and preferentially localizes to and signals from endo-lysosomal compartments. To test this hypothesis, the kinetics of cellular uptake of the compound in Daudi cells using tritiated Vesatolimod (³H-GS-9620) is measured. The kinetics of ³H-GS-9620 accumulation is rapid, reaching concentration-dependent steady-state equilibrium in approximately thirty minutes. Measured intracellular concentration of ³H-Vesatolimod is 5-fold higher than the extracellular concentration of ³H-GS-9620 used to treat cells. Increases in intracellular ³H-Vesatolimod concentrations are roughly proportional with increasing concentrations of ³H-GS-9620.

In Vivo: Single oral doses of Vesatolimod (GS-9620) at 0.3 and 1 mg/kg in uninfected chimpanzees demonstrates a dose- and exposure-related induction of serum IFN-α, select cytokines/chemokines, and IFN-stimulated genes (ISG) in the peripheral blood and liver. Following oral administration at 0.3 (n=3), and 1 mg/kg (n=3 and n=4), Vesatolimod (GS-9620) C_max is 3.6±3.5, 36.8±34.5, and 55.4±81.0 nM, respectively. Peak serum IFN responses occur at 8 h post-dose. The mean peak levels of induced serum IFN-α are 66 and 479 pg/mL at doses of 0.3 and 1 mg/kg, respectively. Vesatolimod (GS-9620) treatment induces ISG transcripts including ISG15, OAS-1, MX1, IP-10 (CXCL10), and I-TAC (CXCL11) in peripheral blood mononuclear cells (PBMC) at 0.3 mg/kg and in both PBMC and the liver at 1 mg/kg.

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