GS-9620(Vesatolimod)

Cas No.:	1228585-88-3
Chemical Name:	6(5H)-Pteridinone,4-amino-2-butoxy-7,8-dihydro-8-[[3-(1-pyrrolidinylmethyl)phenyl]methyl]-
Synonyms:	GS 9620; GS9620
SMILES:	CCCCOC1=NC2=C(C(=N1)N)NC(=O)CN2CC3=CC(=CC=C3)CN4CCCC4
Formula:	C22H30N6O2
M.Wt:	410.51
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Vesatolimod (GS-9620) is a potent, selective and orally active agonist of Toll-Like Receptor (TLR7) with an EC50 of 291 nM.
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 interferon-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) Cmax is 3.6±3.5, 36.8±34.5, and 55.4±81.0 nM, respectively. Peak serum interferon 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[2].
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[1].