Vesatolimod
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MedKoo CAT#: 206456

CAS#: 1228585-88-3

Description: Vesatolimod, also known as GS-9620, is a potent and oral agonist of Toll-like receptor-7 developed for finite treatment of chronic hepatitis B viral (HBV) infection, with the goal of inducing a liver-targeted antiviral effect without inducing the adverse effects associated with current systemic interferon-α (IFN-α) therapies. GS-9620 demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses. GS-9620 can induce a sustained antiviral response in the woodchuck model of CHB.


Chemical Structure

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Vesatolimod
CAS# 1228585-88-3

Theoretical Analysis

MedKoo Cat#: 206456
Name: Vesatolimod
CAS#: 1228585-88-3
Chemical Formula: C22H30N6O2
Exact Mass: 410.24302
Molecular Weight: 410.52
Elemental Analysis: C, 64.37; H, 7.37; N, 20.47; O, 7.79

Price and Availability

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10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
50.0mg USD 450.0 Same day
100.0mg USD 650.0 Same day
200.0mg USD 1050.0 Same day
500.0mg USD 1950.0 Same day
1.0g USD 2950.0 Same day
2.0g USD 4250.0 2 weeks
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Synonym: GS-9620; GS 9620; GS9620; Vesatolimod

IUPAC/Chemical Name: 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one

InChi Key: VFOKSTCIRGDTBR-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C1NC2=C(N)N=C(OCCCC)N=C2N(CC3=CC=CC(CN4CCCC4)=C3)C1

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Vesatolimod (GS-9620) is an agonist of Toll-Like Receptor (TLR7) with an EC50 of 291 nM.
In vitro activity: As shown in Table 1, GS-9620 was inactive against HIV in isolated CD4+ T cells and macrophages up to the highest concentration tested (10 μM) but did show dose-dependent inhibition of HIV-1 replication in complete PBMCs following infection with either HIV-1BaL (EC50 = 536 nM) or HIV-1VSV-G-LUC (EC50 = 953 nM). Although GS-9620-mediated antiretroviral activity varied significantly between individual donors, its antiretroviral potency in PBMCs was enhanced by approximately 35-fold when GS-9620 was added 48 h prior to infection with HIV-1VSV-G-LUC (EC50 = 27 nM). Similar potency improvements were also observed in GS-9620-pretreated PBMCs infected with HIV-1BaL (data not shown). The antiretroviral activity was likely not due to cytotoxicity. A 50% cytotoxic concentration (CC50) value of 22 μM for uninfected activated PBMCs translates to a mean selectivity index (CC50/EC50 ratio) of 815-fold for GS-9620. Reference: Antimicrob Agents Chemother. 2017 Jan; 61(1): e01369-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192112/
In vivo activity: GS-9620 treatment induced marked, sustained reductions in serum WHV DNA noted as early as the first week of treatment. GS-9620 induced reductions in viremia occurred in nearly all GS-9620-treated woodchucks by week 4 (Fig. 3 and Table 2). In contrast, the placebo group had no changes in serum WHV DNA. WHV-infected woodchucks treated QOD for 4 weeks (group 3) had a uniformly marked antiviral response with a mean maximal viral load reduction of 6.2 log10. At the end of the study (week 35), this group had a mean 4.8 log10 reduction in viral load. Mean viral load in this group during weeks 3–35 were significantly reduced compared to pretreatment (all p<0.05) and the placebo control group at weeks 2–35 (all p<0.05). Reference: J Hepatol. 2015 Jun; 62(6): 1237–1245. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439359/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 10.89 26.53
DMSO:PBS (pH 7.2) (1:3) 0.25 0.61
DMF 1.0 2.44
4-methylpyridine 12.0 29.23

Preparing Stock Solutions

The following data is based on the product molecular weight 410.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Tsai A, Irrinki A, Kaur J, Cihlar T, Kukolj G, Sloan DD, Murry JP. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. J Virol. 2017 Mar 29;91(8):e02166-16. doi: 10.1128/JVI.02166-16. PMID: 28179531; PMCID: PMC5375698. 2. Bam RA, Hansen D, Irrinki A, Mulato A, Jones GS, Hesselgesser J, Frey CR, Cihlar T, Yant SR. TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01369-16. doi: 10.1128/AAC.01369-16. PMID: 27799218; PMCID: PMC5192112. 3. Menne S, Tumas DB, Liu KH, Thampi L, AlDeghaither D, Baldwin BH, Bellezza CA, Cote PJ, Zheng J, Halcomb R, Fosdick A, Fletcher SP, Daffis S, Li L, Yue P, Wolfgang GH, Tennant BC. Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B. J Hepatol. 2015 Jun;62(6):1237-45. doi: 10.1016/j.jhep.2014.12.026. Epub 2015 Jan 2. PMID: 25559326; PMCID: PMC4439359. 4. Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, Fosdick A, Frey CR, Zheng J, Wolfgang G, Halcomb RL, Tumas DB. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology. 2013 Jun;144(7):1508-17, 1517.e1-10. doi: 10.1053/j.gastro.2013.02.003. Epub 2013 Feb 13. PMID: 23415804; PMCID: PMC3691056.
In vitro protocol: 1. Tsai A, Irrinki A, Kaur J, Cihlar T, Kukolj G, Sloan DD, Murry JP. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. J Virol. 2017 Mar 29;91(8):e02166-16. doi: 10.1128/JVI.02166-16. PMID: 28179531; PMCID: PMC5375698. 2. Bam RA, Hansen D, Irrinki A, Mulato A, Jones GS, Hesselgesser J, Frey CR, Cihlar T, Yant SR. TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01369-16. doi: 10.1128/AAC.01369-16. PMID: 27799218; PMCID: PMC5192112.
In vivo protocol: 1. Menne S, Tumas DB, Liu KH, Thampi L, AlDeghaither D, Baldwin BH, Bellezza CA, Cote PJ, Zheng J, Halcomb R, Fosdick A, Fletcher SP, Daffis S, Li L, Yue P, Wolfgang GH, Tennant BC. Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B. J Hepatol. 2015 Jun;62(6):1237-45. doi: 10.1016/j.jhep.2014.12.026. Epub 2015 Jan 2. PMID: 25559326; PMCID: PMC4439359. 2. Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, Fosdick A, Frey CR, Zheng J, Wolfgang G, Halcomb RL, Tumas DB. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology. 2013 Jun;144(7):1508-17, 1517.e1-10. doi: 10.1053/j.gastro.2013.02.003. Epub 2013 Feb 13. PMID: 23415804; PMCID: PMC3691056.

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1: Cohen J. Drug flushes out hidden AIDS virus. Science. 2015 Mar 6;347(6226):1056. doi: 10.1126/science.347.6226.1056-a. PubMed PMID: 25745141.

2: Gane EJ, Lim YS, Gordon SC, Visvanathan K, Sicard E, Fedorak RN, Roberts S, Massetto B, Ye Z, Pflanz S, Garrison KL, Gaggar A, Mani Subramanian G, McHutchison JG, Kottilil S, Freilich B, Coffin CS, Cheng W, Kim YJ. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection. J Hepatol. 2015 Aug;63(2):320-8. doi: 10.1016/j.jhep.2015.02.037. Epub 2015 Feb 27. PubMed PMID: 25733157.

3: Menne S, Tumas DB, Liu KH, Thampi L, AlDeghaither D, Baldwin BH, Bellezza CA, Cote PJ, Zheng J, Halcomb R, Fosdick A, Fletcher SP, Daffis S, Li L, Yue P, Wolfgang GH, Tennant BC. Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B. J Hepatol. 2015 Jun;62(6):1237-45. doi: 10.1016/j.jhep.2014.12.026. Epub 2015 Jan 2. PubMed PMID: 25559326; PubMed Central PMCID: PMC4439359.

4: Lawitz E, Gruener D, Marbury T, Hill J, Webster L, Hassman D, Nguyen AH, Pflanz S, Mogalian E, Gaggar A, Massetto B, Subramanian GM, McHutchison JG, Jacobson IM, Freilich B, Rodriguez-Torres M. Safety, pharmacokinetics and pharmacodynamics of the oral Toll-like receptor 7 agonist GS-9620 in treatment-naive patients with chronic hepatitis C. Antivir Ther. 2014 Aug 8. doi: 10.3851/IMP2845. [Epub ahead of print] PubMed PMID: 25105516.

5: Fosdick A, Zheng J, Pflanz S, Frey CR, Hesselgesser J, Halcomb RL, Wolfgang G, Tumas DB. Pharmacokinetic and pharmacodynamic properties of GS-9620, a novel Toll-like receptor 7 agonist, demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses. J Pharmacol Exp Ther. 2014 Jan;348(1):96-105. doi: 10.1124/jpet.113.207878. Epub 2013 Oct 16. PubMed PMID: 24133297.

6: Roethle PA, McFadden RM, Yang H, Hrvatin P, Hui H, Graupe M, Gallagher B, Chao J, Hesselgesser J, Duatschek P, Zheng J, Lu B, Tumas DB, Perry J, Halcomb RL. Identification and optimization of pteridinone Toll-like receptor 7 (TLR7) agonists for the oral treatment of viral hepatitis. J Med Chem. 2013 Sep 26;56(18):7324-33. doi: 10.1021/jm400815m. Epub 2013 Sep 9. PubMed PMID: 23961878.

7: Zoulim F, Luangsay S, Durantel D. Targeting innate immunity: a new step in the development of combination therapy for chronic hepatitis B. Gastroenterology. 2013 Jun;144(7):1342-4. doi: 10.1053/j.gastro.2013.04.028. PubMed PMID: 23710602.

8: Rosania K. Relying on chimpanzees for hepatitis research. Lab Anim (NY). 2013 Jun;42(6):188. doi: 10.1038/laban.317. PubMed PMID: 23689445.

9: Lopatin U, Wolfgang G, Tumas D, Frey CR, Ohmstede C, Hesselgesser J, Kearney B, Moorehead L, Subramanian GM, McHutchison JG. Safety, pharmacokinetics and pharmacodynamics of GS-9620, an oral Toll-like receptor 7 agonist. Antivir Ther. 2013;18(3):409-18. doi: 10.3851/IMP2548. Epub 2013 Feb 15. PubMed PMID: 23416308.

10: Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, Fosdick A, Frey CR, Zheng J, Wolfgang G, Halcomb RL, Tumas DB. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology. 2013 Jun;144(7):1508-17, 1517.e1-10. doi: 10.1053/j.gastro.2013.02.003. Epub 2013 Feb 13. PubMed PMID: 23415804; PubMed Central PMCID: PMC3691056.