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GS-9620 Vesatolimod 1228585-88-3
GS-9620 is an orally active TLR7 agonist with EC50 of 291 nM. [1]
| Cas No. | 1228585-88-3 |
Synonyms | Vesatolimod |
Chemical Name | 4-amino-2-butoxy-8-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5,7-dihydropteridin-6-one |
Canonical SMILES | CCCCOC1=NC2=C(C(=N1)N)NC(=O)CN2CC3=CC(=CC=C3)CN4CCCC4 |
Formula | C22H30N6O2 |
M.Wt | 410.51 |
Solubility | ≥ 20.55 mg/mL in DMSO, ≥ 9.9 mg/mL in EtOH with ultrasonic and warming |
Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. |
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. | |
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Toll-like receptor 7 (TLR7) is a pathogen recognition receptor which plays an important role in the detection of, and the innate immune response to, pathogens. TLR7 signaling is predominantly activated by viral single-stranded RNA and is localized within the endolysosomal compartments of plasmacytoid dendritic cells (pDCs) and B lymphocytes in humans and non-human primates. Activation of pDCs plays an important role in the progress of innate response to viral pathogens and are involved in the majority of type I interferon (IFN) production during the acute phase of an infection by viruses. The induction and secretion of endogenous IFNs, including IFN-α and IFN- β, also induce the development of an efficient adaptive immunological response. Interferons induce the transcription of interferon-stimulated genes (ISGs) which generate an antiviral state within cells, as well as induce the production of other cytokines and chemokines which facilitate intercellular communication and cellular trafficking. GS-9620 could activate TLR7 signaling in immune cells to induce clearance of virus infected cells. [1, 2]
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. [1]
GS-9620 was administered to HBV infected chimpanzees for 8 weeks with an interval of 1 week. Consequently, serum concentrations of HBV surface antigen and HBV antigen, and the number of HBV antigen–positive hepatocytes, were decreased as hepatocyte apoptosis increased. In a phase 1 clinical trial to evaluate the safety and tolerability of GS-9620, treatment of GS-9620 results in dose dependent increases in select cytokines, chemokines, and ISGs beginning at 2mg and is safe in a single dose up to 12mg. Increases in percentages of immunocytes, like T cells, B cells and NK cells, expressing CD69 were also noted in subjects receiving GS-9620 treatment. [2, 3]
References:
[1]. Turnas P, Zheng X, Lu B, et al. 1129 Preclinical characterization of GS-9620, a potent and selective oral TLR7 agonist[J]. Journal of Hepatology, 2011, 54: S446-S447.
[2]. Lanford R E, Guerra B, Chavez D, et al. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees[J]. Gastroenterology, 2013, 144(7): 1508-1517. e10.
[3]. Lopatin U, Wolfgang G, Kimberlin R, et al. 737 A phase-i, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single escalating oral doses of GS-9620 in healthy subjects[J]. Journal of Hepatology, 2011, 54: S296.
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.