| Synonyms |
4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one; GS-9620; GS9620; Vesatolimod |
| IUPAC Name |
4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one |
| Molecular Weight |
410.51 |
| Molecular Formula |
C22H30N6O2 |
| Canonical SMILES |
CCCCOC1=NC2=C(C(=N1)N)NC(=O)CN2CC3=CC(=CC=C3)CN4CCCC4 |
| InChI |
1S/C22H30N6O2/c1-2-3-11-30-22-25-20(23)19-21(26-22)28(15-18(29)24-19)14-17-8-6-7-16(12-17)
13-27-9-4-5-10-27/h6-8,12H,2-5,9-11,13-15H2,1H3,(H,24,29)(H2,23,25,26) |
| InChIKey |
VFOKSTCIRGDTBR-UHFFFAOYSA-N |
| Purity |
99.90% |
| Density |
1.2±0.1 g/cm3 |
| Solubility |
Soluble in DMSO, not in water |
| Appearance |
Solid powder |
| Application |
Antiviral Agents |
| Shelf Life |
>2 years if stored properly |
| Storage |
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Animal Admin |
Chimpanzee Chimpanzees are used. The trial design includes 4 weeks of pre-study evaluation (Day-28, -13 and just prior to first dose) and two cycles of oral Vesatolimod (GS-9620) treatment every other day three times per week for 4 weeks with one cycle at 1 mg/kg, and, after a one week rest, a second cycle at 2 mg/kg. Animals are also intensely monitored for 14 weeks after treatment to assess tolerability and durability of response. |
| Assay |
Daudi cells are incubated for indicated times with varying concentrations [3H]Vesatolimod (GS-9620) (0.7μCi/mL). Cell associated radioactivity is extracted with ice cold 80% ethanol and measured using liquid scintillation counting. The total amount of Vesatolimod in cells is calculated from a calibration curve for Vesatolimod (GS-9620) mass versus radioactivity. Cell volume is measured. |
| Complexity |
558 |
| Exact Mass |
410.24302422 |
| Index Of Refraction |
1.622 |
| 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 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. |
| PSA |
100.10000 |
| Target |
EC50: 291 nM (TLR7), 9 μM (TLR8) |
| XLogP3-AA |
2.7 |
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