GS-441524 | FIP inhibitor | CAS#1191237-69-0

MedKoo Cat#: 555299 | Name: GS-441524

Description:

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

GS-441524 is a potent inhibitor of feline infectious peritonitis (FIP) virus with an EC50 of 0.78 μM.. GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. Note: GS-441524 is an active metabolite of Remdesivir.

Chemical Structure

GS-441524

CAS#1191237-69-0 (free base)

Theoretical Analysis

MedKoo Cat#: 555299

Name: GS-441524

CAS#: 1191237-69-0 (free base)

Chemical Formula: C12H13N5O4

Exact Mass: 291.0968

Molecular Weight: 291.10

Elemental Analysis: C, 49.48; H, 4.50; N, 24.04; O, 21.97

Price and Availability

Size	Price	Availability
100mg	USD 90.00	Ready to ship
200mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 450.00	Ready to ship
5g	USD 1,150.00	Ready to ship
10g	USD 1,950.00	Ready to ship
100g	USD 9,950.00	Ready to ship

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Related CAS #

1191237-69-0 (free base) 2378280-82-9 (HCl) 2378280-83-0 (sulfate) 1191237-69-0 (solution)

Synonym

GS-441524; GS 441524; GS441524; Remdesivir-metabolite, GS-5734-metabolite; GS5734-metabolite; GS 5734-metabolite;

IUPAC/Chemical Name

(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile

InChi Key

BRDWIEOJOWJCLU-LTGWCKQJSA-N

InChi Code

InChI=1S/C12H13N5O4/c13-4-12(10(20)9(19)7(3-18)21-12)8-2-1-6-11(14)15-5-16-17(6)8/h1-2,5,7,9-10,18-20H,3H2,(H2,14,15,16)/t7-,9-,10-,12+/m1/s1

SMILES Code

N#C[C@@]1(C2=CC=C3C(N)=NC=NN32)O[C@H](CO)[C@@H](O)[C@H]1O

Appearance

Solid powder

Purity

>97% (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

Shelf Life

>3 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

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Note: Chemical structure was from MBio. 2018 Mar 6;9(2). pii: e00221-18. doi: 10.1128/mBio.00221-18. https://mbio.asm.org/content/9/2/e00221-18/figures-only For preparation of GS-441524 stock solution, customer may use below protocol, which was published https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435921/ Drug preparation GS-441524 was diluted to a concentration of 10 or 15 mg/ml in 5% ethanol, 30% propylene glycol, 45% PEG 400, 20% water (pH 1.5 with HCl). The mixture was placed in sterile 50 ml glass injection bottles, agitated until in suspension, and then placed in a sonicated water bath for 5–20 mins until clear. The diluted drug was refrigerated and used within 3–4 weeks.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R12B23

View CoA: current batch, Lot#C23R12B13

View CoA: current batch, Lot#C21R06B17

QC Data

View QC data: current batch, Lot#C20R12B23

View QC data: current batch, Lot#C21R06B17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GS-441524, predominant metabolite of Remdesivir and superior to Remdesivir against COVID-19, shows comparable efficacy in cell-based models of primary human lung and cat cells infected with coronavirus.

In vitro activity:

The antiviral potential of GS-441524 against African swine fever virus (ASFV) was demonstrated in porcine alveolar macrophages (PAMs). GS-441524 exhibited a dose-dependent inhibition of ASFV infection, particularly during the early stages of viral replication. GS-441524 did not elevate the levels of antiviral cytokines or ATP in PAMs. Conversely, an elevated concentration of natural ATP in PAMs resulted in increased ASFV replication, counteracting the inhibitory effects of GS-441524 in a dose-dependent manner. Reference: Antiviral Res. 2021 Jul;191:105081. https://pubmed.ncbi.nlm.nih.gov/33945807/

In vivo activity:

This study supports the development of GS-441524 (RVn) phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Reference: J Med Chem. 2023 Apr 27;66(8):5802-5819. https://pubmed.ncbi.nlm.nih.gov/37040439/

	Solvent	mg/mL	mM
Solubility
	DMSO	80.0	274.91

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 291.10 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:

In vitro protocol:

1. Murphy BG, Perron M, Murakami E, Bauer K, Park Y, Eckstrand C, Liepnieks M, Pedersen NC. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet Microbiol. 2018 Jun;219:226-233. doi: 10.1016/j.vetmic.2018.04.026. Epub 2018 Apr 22. PMID: 29778200; PMCID: PMC7117434. 2. Huang Z, Gong L, Zheng Z, Gao Q, Chen X, Chen Y, Chen X, Xu R, Zheng J, Xu Z, Zhang S, Wang H, Zhang G. GS-441524 inhibits African swine fever virus infection in vitro. Antiviral Res. 2021 May 1;191:105081. doi: 10.1016/j.antiviral.2021.105081. Epub ahead of print. PMID: 33945807.

In vivo protocol:

1. Murphy BG, Perron M, Murakami E, Bauer K, Park Y, Eckstrand C, Liepnieks M, Pedersen NC. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet Microbiol. 2018 Jun;219:226-233. doi: 10.1016/j.vetmic.2018.04.026. Epub 2018 Apr 22. PMID: 29778200; PMCID: PMC7117434. 2. Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg. 2019 Apr;21(4):271-281. doi: 10.1177/1098612X19825701. Epub 2019 Feb 13. PMID: 30755068; PMCID: PMC6435921.

1: Shafer RW. A SARS-CoV-2 antiviral therapy score card. Glob Health Med. 2020 Dec 31;2(6):346-349. doi: 10.35772/ghm.2020.01082. PMID: 33409413; PMCID: PMC7780285. 2: Hanafin PO, Jermain B, Hickey AJ, Kabanov AV, Kashuba AD, Sheahan TP, Rao GG. A Mechanism-based Pharmacokinetic Model of Remdesivir Leveraging Interspecies Scaling to Simulate COVID-19 Treatment in Humans. CPT Pharmacometrics Syst Pharmacol. 2020 Dec 9. doi: 10.1002/psp4.12584. Epub ahead of print. PMID: 33296558. 3: Nili A, Farbod A, Neishabouri A, Mozafarihashjin M, Tavakolpour S, Mahmoudi H. Remdesivir: A beacon of hope from Ebola virus disease to COVID-19. Rev Med Virol. 2020 Nov;30(6):1-13. doi: 10.1002/rmv.2133. Epub 2020 Jul 30. PMID: 33210457. 4: Dickinson PJ. Coronavirus Infection of the Central Nervous System: Animal Models in the Time of COVID-19. Front Vet Sci. 2020 Oct 23;7:584673. doi: 10.3389/fvets.2020.584673. PMID: 33195610; PMCID: PMC7644464. 5: Jung LS, Gund TM, Narayan M. Comparison of Binding Site of Remdesivir and Its Metabolites with NSP12-NSP7-NSP8, and NSP3 of SARS CoV-2 Virus and Alternative Potential Drugs for COVID-19 Treatment. Protein J. 2020 Dec;39(6):619-630. doi: 10.1007/s10930-020-09942-9. Epub 2020 Nov 13. PMID: 33185784; PMCID: PMC7662030. 6: Davis MR, Pham CU, Cies JJ. Remdesivir and GS-441524 plasma concentrations in patients with end-stage renal disease on haemodialysis. J Antimicrob Chemother. 2020 Nov 5:dkaa472. doi: 10.1093/jac/dkaa472. Epub ahead of print. PMID: 33152758. 7: Izes AM, Yu J, Norris JM, Govendir M. Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats. Vet Q. 2020 Dec;40(1):322-330. doi: 10.1080/01652176.2020.1845917. PMID: 33138721; PMCID: PMC7671703. 8: Sahakijpijarn S, Moon C, Koleng JJ, Christensen DJ, Williams Iii RO. Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing. Pharmaceutics. 2020 Oct 22;12(11):1002. doi: 10.3390/pharmaceutics12111002. PMID: 33105618; PMCID: PMC7690377. 9: Yan VC, Muller FL. Captisol and GS-704277, but Not GS-441524, Are Credible Mediators of Remdesivir's Nephrotoxicity. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01920-20. doi: 10.1128/AAC.01920-20. PMID: 32988821; PMCID: PMC7674034. 10: Lê MP, Le Beller C, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, Peytavin G. Reply to Yan and Muller, "Captisol and GS-704277, but Not GS-441524, Are Credible Mediators of Remdesivir's Nephrotoxicity". Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01937-20. doi: 10.1128/AAC.01937-20. PMID: 32988815; PMCID: PMC7674048. 11: Paltrinieri S, Giordano A, Stranieri A, Lauzi S. Feline infectious peritonitis (FIP) and coronavirus disease 19 (COVID-19): Are they similar? Transbound Emerg Dis. 2020 Sep 28:10.1111/tbed.13856. doi: 10.1111/tbed.13856. Epub ahead of print. PMID: 32985113; PMCID: PMC7537058. 12: Schooley RT, Carlin AF, Beadle JR, Valiaeva N, Zhang XQ, Garretson AF, Smith VI, Murphy J, Hostetler KY. Rethinking Remdesivir: Synthesis of Lipid Prodrugs that Substantially Enhance Anti-Coronavirus Activity. bioRxiv [Preprint]. 2020 Aug 27:2020.08.26.269159. doi: 10.1101/2020.08.26.269159. PMID: 32869033; PMCID: PMC7457622. 13: Lê MP, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, Peytavin G. Removal of Remdesivir's Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19. Antimicrob Agents Chemother. 2020 Oct 20;64(11):e01521-20. doi: 10.1128/AAC.01521-20. PMID: 32868327; PMCID: PMC7577145. 14: Pruijssers AJ, George AS, Schäfer A, Leist SR, Gralinksi LE, Dinnon KH 3rd, Yount BL, Agostini ML, Stevens LJ, Chappell JD, Lu X, Hughes TM, Gully K, Martinez DR, Brown AJ, Graham RL, Perry JK, Du Pont V, Pitts J, Ma B, Babusis D, Murakami E, Feng JY, Bilello JP, Porter DP, Cihlar T, Baric RS, Denison MR, Sheahan TP. Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice. Cell Rep. 2020 Jul 21;32(3):107940. doi: 10.1016/j.celrep.2020.107940. Epub 2020 Jul 7. PMID: 32668216; PMCID: PMC7340027. 15: Yan VC, Muller FL. Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment. ACS Med Chem Lett. 2020 Jun 23;11(7):1361-1366. doi: 10.1021/acsmedchemlett.0c00316. PMID: 32665809; PMCID: PMC7315846. 16: Tempestilli M, Caputi P, Avataneo V, Notari S, Forini O, Scorzolini L, Marchioni L, Ascoli Bartoli T, Castilletti C, Lalle E, Capobianchi MR, Nicastri E, D'Avolio A, Ippolito G, Agrati C; COVID 19 INMI Study Group. Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19. J Antimicrob Chemother. 2020 Oct 1;75(10):2977-2980. doi: 10.1093/jac/dkaa239. PMID: 32607555; PMCID: PMC7337789. 17: Humeniuk R, Mathias A, Cao H, Osinusi A, Shen G, Chng E, Ling J, Vu A, German P. Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects. Clin Transl Sci. 2020 Sep;13(5):896-906. doi: 10.1111/cts.12840. Epub 2020 Aug 5. PMID: 32589775; PMCID: PMC7361781. 18: Alvarez JC, Moine P, Etting I, Annane D, Larabi IA. Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient. Clin Chem Lab Med. 2020 Jun 22;58(9):1461-1468. doi: 10.1515/cclm-2020-0612. PMID: 32573468. 19: Dickinson PJ, Bannasch M, Thomasy SM, Murthy VD, Vernau KM, Liepnieks M, Montgomery E, Knickelbein KE, Murphy B, Pedersen NC. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. J Vet Intern Med. 2020 Jul;34(4):1587-1593. doi: 10.1111/jvim.15780. Epub 2020 May 22. PMID: 32441826; PMCID: PMC7379040. 20: Avataneo V, de Nicolò A, Cusato J, Antonucci M, Manca A, Palermiti A, Waitt C, Walimbwa S, Lamorde M, di Perri G, D'Avolio A. Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS- CoV-2/COVID-19 and Ebola virus disease. J Antimicrob Chemother. 2020 Jul 1;75(7):1772-1777. doi: 10.1093/jac/dkaa152. PMID: 32361744; PMCID: PMC7197584.

1. Jiashu Xie, Zhengqiang Wang, Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment, Acta Pharmaceutica Sinica B, 2021,(https://doi.org/10.1016/j.apsb.2021.03.028).