| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Vesatolimod (formerly known as GS9620; GS-9620) is a novel potent, selective and orally bioactive small molecule agonist of Toll-like receptor 7 (TLR-7) with antiviral activity. It activates TLR-7 with an EC50 of 291 nM. Vesatolimod has the potential for the treatment of chronic hepatitis B viral (HBV) infection. GS-9620 selectively induces IFN-α, cytokines and chemokines. The minimum effective concentrations for IFN-α induction were similar in pDCs and in PBMCs from HCV-positive donors. GS-9620 demonstrates an EC50 of 291 nM for human TLR7, which is 30-fold selectivity over TLR8 with EC50 of 9 μM.
| ln Vitro |
Vesatolimod (GS-9620) enters cells quickly, localizes to endo-lysosomal compartments preferentially, and communicates from these areas. The kinetics of the compound's cellular absorption in Daudi cells using tritiated Vesatolimod (3H-GS-9620) is studied in order to test this notion. The buildup of 3H-GS-9620 proceeds quickly; it takes about thirty minutes to attain a concentration-dependent steady-state equilibrium. The concentration of 3H-Vesatolimod measured within cells is five times more than the concentration of 3H-GS-9620 used outside cells for treatment. Elevations in 3H-GS-9620 concentrations are approximately correlated with increases in intracellular 3H-Vesatolimod concentrations[1].
|
||
|---|---|---|---|
| ln Vivo |
In uninfected chimpanzees, single oral doses of Vesatolimod (GS-9620) at 0.3 and 1 mg/kg show a dose- and exposure-related elevation of serum IFN-α, some cytokines/chemokines, and IFN-stimulated genes (ISG) in the liver and peripheral circulation. The Cmax values of Vesatolimod (GS-9620) after oral administration at 0.3 (n=3) and 1 mg/kg (n=3 and n=4) are 3.6±3.5, 36.8±34.5, and 55.4± 81.0 nM, respectively. After 8 hours, serum IFN responses reach their peak. At dosages of 0.3 and 1 mg/kg, the mean peak values of induced serum IFN-α are 479 and 66 pg/mL, respectively. Treatment with vesatolimod (GS-9620) produces ISG transcripts in peripheral blood mononuclear cells (PBMC) at 0.3 mg/kg and in the liver at 1 mg/kg. These transcripts include ISG15, OAS-1, MX1, IP-10 (CXCL10), and I-TAC (CXCL11)[2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Rebbapragada I, et al. Molecular Determinants of GS-9620-Dependent TLR7 Activation. PLoS One. 2016 Jan 19;11(1):e0146835.
[2]. Lanford RE, et al. GS-9620, an Oral Agonist of Toll-Like Receptor-7, Induces Prolonged Suppression of Hepatitis B Virus in Chronically Infected Chimpanzees. Gastroenterology. 2013 Feb 13. pii: S0016-5085(13)00169-8. [3]. D Tumas, et al. Preclinical Characterization of GS-9620, A Potent and Selective Oral TLR7 Agonist |
| Molecular Formula |
C22H30N6O2
|
|
|---|---|---|
| Molecular Weight |
410.52
|
|
| CAS # |
1228585-88-3
|
|
| Related CAS # |
1228585-88-3;1454806-18-8 (HCl);
|
|
| SMILES |
O=C1NC2=C(N)N=C(OCCCC)N=C2N(CC3=CC=CC(CN4CCCC4)=C3)C1
|
|
| Synonyms |
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4359 mL | 12.1797 mL | 24.3593 mL | |
| 5 mM | 0.4872 mL | 2.4359 mL | 4.8719 mL | |
| 10 mM | 0.2436 mL | 1.2180 mL | 2.4359 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 GS-9620 rapidly distributes to and signals through the endo-lysosomal compartments. Fig 3. Amino acid changes due to described single nucleotide polymorphisms (SNPs) do not impact GS-9620-dependent TLR7 activation.PLoS One.2016 Jan 19;11(1):e0146835. |
|---|
 Structure-based mutational analysis identifies residues in TLR7 that are essential for GS-9620 in vitro activity.. From: Molecular Determinants of GS-9620-Dependent TLR7 Activation.PLoS One.2016 Jan 19;11(1):e0146835. |
 GS-9620 induces phosphorylation of NF-κB and Akt in pDCs.
TLR7 dimers exist independent of GS-9620 binding.PLoS One.2016 Jan 19;11(1):e0146835. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
