GS-441524
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MedKoo CAT#: 555299

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

Description: 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

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GS-441524
CAS# 1191237-69-0 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555299
Name: GS-441524
CAS#: 1191237-69-0 (free base)
Chemical Formula: C12H13N5O4
Exact Mass: 291.10
Molecular Weight: 291.100
Elemental Analysis: C, 49.48; H, 4.50; N, 24.04; O, 21.97

Price and Availability

Size Price Availability Quantity
100mg USD 90 Ready to ship
200mg USD 150 Ready to ship
500mg USD 250 Ready to ship
1g USD 450 Ready to ship
5g USD 1150 Ready to ship
10g USD 1950 Ready to ship
100g USD 9950 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.

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 80.0 274.91

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.

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:
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.

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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.


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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.


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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).