Vesatolimod | GS-9620 | CAS#1228585-88-3 | TLR7 Agonist

MedKoo Cat#: 206456 | Name: Vesatolimod

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Vesatolimod

CAS#1228585-88-3 (free base)

Theoretical Analysis

MedKoo Cat#: 206456

Name: Vesatolimod

CAS#: 1228585-88-3 (free base)

Chemical Formula: C22H30N6O2

Exact Mass: 410.2430

Molecular Weight: 410.52

Elemental Analysis: C, 64.37; H, 7.37; N, 20.47; O, 7.79

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 700.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

1228585-88-3 (free base) 1454806-18-8 (HCl)

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB70315

QC Data

View QC data: current batch, Lot#CRB70315

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.9	26.53
	DMSO:PBS (pH 7.2) (1:3)	0.3	0.61
	DMF	1.0	2.44
	4-methylpyridine	12.0	29.23

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Daly MB, Dinh C, Holder A, Rudolph D, Ruone S, Swaims-Kohlmeier A, Khalil G, Sharma S, Mitchell J, Condrey J, Kim D, Pan Y, Curtis K, Williams P, Spreen W, Heneine W, García-Lerma JG. SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity. Nat Commun. 2024 Dec 4;15(1):10550. doi: 10.1038/s41467-024-54783-0. PMID: 39632836; PMCID: PMC11618496. 2: Riddler SA, Benson CA, Brinson C, Deeks SG, DeJesus E, Mills A, Para MF, Ramgopal MN, Cai Y, Zheng Y, Zhang L, Jiang W, Liu X, Verrill D, Lim D, de Vries CR, Wallin JJ, Vendrame E, SenGupta D. A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod. Infect Dis Ther. 2024 Nov;13(11):2285-2299. doi: 10.1007/s40121-024-01034-w. Epub 2024 Sep 15. PMID: 39278975; PMCID: PMC11499514. 3: Abdel-Mohsen M, Deeks S, Giron L, Hong KY, Goldman A, Zhang L, Huang SSY, Verrill D, Guo S, Selzer L, de Vries CR, Vendrame E, SenGupta D, Wallin JJ, Cai Y. Circulating immune and plasma biomarkers of time to HIV rebound in HIV controllers treated with vesatolimod. Front Immunol. 2024 Jun 24;15:1405348. doi: 10.3389/fimmu.2024.1405348. PMID: 38979421; PMCID: PMC11229794. 4: Cai Y, Podlaha O, Deeks SG, Brinson C, Ramgopal MN, DeJesus E, Mills A, Shalit P, Abdel-Mohsen M, Zhang L, de Vries CR, Vendrame E, SenGupta D, Wallin JJ. HIV rebound in HIV controllers is associated with a specific fecal microbiome profile. Eur J Immunol. 2024 Aug;54(8):e2350809. doi: 10.1002/eji.202350809. Epub 2024 May 10. PMID: 38727191. 5: Li H, Huang Y, Yang Q, Zhang Z, Shen S, Guo H, Wei W. Pharmacological activation of TLR7 exerts inhibition on the replication of EV-D68 in respiratory cells. J Virol. 2024 Jun 13;98(6):e0043424. doi: 10.1128/jvi.00434-24. Epub 2024 May 1. PMID: 38690875; PMCID: PMC11237570. 6: Mudd JC. Quantitative and Qualitative Distinctions between HIV-1 and SIV Reservoirs: Implications for HIV-1 Cure-Related Studies. Viruses. 2024 Mar 27;16(4):514. doi: 10.3390/v16040514. PMID: 38675857; PMCID: PMC11054464. 7: Kadiyala GN, Telwatte S, Wedrychowski A, Janssens J, Kim SJ, Kim P, Deeks S, Wong JK, Yukl SA. Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules. AIDS. 2024 Jul 15;38(9):1281-1291. doi: 10.1097/QAD.0000000000003908. Epub 2024 Apr 20. PMID: 38626436; PMCID: PMC11216394. 8: Jiang X, Song Y, Fang J, Yang X, Mu S, Zhang J. Corrigendum to "Neuroprotective effect of Vesatolimod in an experimental autoimmune encephalomyelitis mice model" [Int. Immunopharmacol. 116 (2023) 109717]. Int Immunopharmacol. 2024 Feb 15;128:111448. doi: 10.1016/j.intimp.2023.111448. Epub 2024 Jan 7. Erratum for: Int Immunopharmacol. 2023 Mar;116:109717. doi: 10.1016/j.intimp.2023.109717. PMID: 38191277. 9: Omer I, Abuthiyab N, Al-Omari B, Aletani T, Betar M, Alzaid N, Hakami AY. Efficacy and safety of vesatolimod in chronic hepatitis B: A systematic review and meta-analysis. Medicine (Baltimore). 2023 Apr 21;102(16):e33609. doi: 10.1097/MD.0000000000033609. PMID: 37083786; PMCID: PMC10118312. 10: Mori T, Yoshio S, Yoshikawa S, Tsustui Y, Sakata T, Yoshida Y, Sakamoto Y, Kawai H, Osawa Y, Yamazoe T, Aoki Y, Fletcher SP, Kanto T. Toll-like receptor 7 agonist, GS-986, is an immune-stimulant inducing follicular helper T cells and expanding HBs antigen-specific B cells in vitro. Liver Int. 2023 Jun;43(6):1213-1224. doi: 10.1111/liv.15568. Epub 2023 Apr 8. PMID: 37029645. 11: Usero L, Leal L, Gómez CE, Miralles L, Aurrecoechea E, Esteban I, Torres B, Inciarte A, Perdiguero B, Esteban M, García F, Plana M. The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses. Vaccines (Basel). 2023 Jan 28;11(2):286. doi: 10.3390/vaccines11020286. PMID: 36851164; PMCID: PMC9961394. 12: Jiang X, Song Y, Fang J, Yang X, Mu S, Zhang J. Neuroprotective effect of Vesatolimod in an experimental autoimmune encephalomyelitis mice model. Int Immunopharmacol. 2023 Mar;116:109717. doi: 10.1016/j.intimp.2023.109717. Epub 2023 Feb 2. Erratum in: Int Immunopharmacol. 2024 Feb 15;128:111448. doi: 10.1016/j.intimp.2023.111448. PMID: 36738672. 13: Liu Y, Diamond SL. Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow. J Immunol Res. 2023 Jan 17;2023:1884439. doi: 10.1155/2023/1884439. PMID: 36703865; PMCID: PMC9873445. 14: Lee G, Kang HR, Kim A, Park JH, Lee MJ, Kim SM. Antiviral effect of vesatolimod (GS-9620) against foot-and-mouth disease virus both in vitro and invivo. Antiviral Res. 2022 Sep;205:105384. doi: 10.1016/j.antiviral.2022.105384. Epub 2022 Jul 19. PMID: 35863499. 15: Walker-Sperling VEK, Mercado NB, Chandrashekar A, Borducchi EN, Liu J, Nkolola JP, Lewis M, Murry JP, Yang Y, Geleziunas R, Robb ML, Michael NL, Pau MG, Wegmann F, Schuitemaker H, Fray EJ, Kumar MR, Siliciano JD, Siliciano RF, Barouch DH. Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques. Nat Commun. 2022 Jun 16;13(1):3463. doi: 10.1038/s41467-022-31196-5. PMID: 35710819; PMCID: PMC9203527. 16: Ventura JD, Nkolola JP, Chandrashekar A, Borducchi EN, Liu J, Mercado NB, Hope DL, Giffin VM, McMahan K, Geleziunas R, Murry JP, Yang Y, Lewis MG, Pau MG, Wegmann F, Schuitemaker H, Fray EJ, Kumar MR, Siliciano JD, Siliciano RF, Robb ML, Michael NL, Barouch DH. Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques. NPJ Vaccines. 2022 May 18;7(1):53. doi: 10.1038/s41541-022-00477-x. PMID: 35585080; PMCID: PMC9117189. 17: Moldt B, Chandrashekar A, Borducchi EN, Nkolola JP, Stephenson H, Nagel M, Hung M, Goldsmith J, Pace CS, Carr B, Thomsen ND, Blair WS, Geleziunas R, Barouch DH. HIV envelope antibodies and TLR7 agonist partially prevent viral rebound in chronically SHIV-infected monkeys. PLoS Pathog. 2022 Apr 22;18(4):e1010467. doi: 10.1371/journal.ppat.1010467. PMID: 35452496; PMCID: PMC9067686. 18: Suresh M, Li B, Huang X, Korolowicz KE, Murreddu MG, Gudima SO, Menne S. Agonistic Activation of Cytosolic DNA Sensing Receptors in Woodchuck Hepatocyte Cultures and Liver for Inducing Antiviral Effects. Front Immunol. 2021 Oct 4;12:745802. doi: 10.3389/fimmu.2021.745802. PMID: 34671360; PMCID: PMC8521114. 19: SenGupta D, Brinson C, DeJesus E, Mills A, Shalit P, Guo S, Cai Y, Wallin JJ, Zhang L, Humeniuk R, Begley R, Geleziunas R, Mellors J, Wrin T, Jones N, Milush J, Ferre AL, Shacklett BL, Laird GM, Moldt B, Vendrame E, Brainard DM, Ramgopal M, Deeks SG. The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy. Sci Transl Med. 2021 Jun 23;13(599):eabg3071. doi: 10.1126/scitranslmed.abg3071. PMID: 34162752. 20: Díaz-Carballo D, Saka S, Acikelli AH, Homp E, Erwes J, Demmig R, Klein J, Schröer K, Malak S, D'Souza F, Noa-Bolaño A, Menze S, Pano E, Andrioff S, Teipel M, Dammann P, Klein D, Nasreen A, Tannapfel A, Grandi N, Tramontano E, Ochsenfarth C, Strumberg D. Enhanced antitumoral activity of TLR7 agonists via activation of human endogenous retroviruses by HDAC inhibitors. Commun Biol. 2021 Mar 3;4(1):276. doi: 10.1038/s42003-021-01800-3. PMID: 33658617; PMCID: PMC7930250.