GS 441524

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.

Product information

CAS Number: 1191237-69-0

Molecular Weight: 291.26

Formula: C12H13N5O4

Synonym:

GS-441524

Remdesivir-metabolite

GS-5734-metabolite

GS  441524

GS441524

GS5734-metabolite

GS 5734-metabolite

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

Smiles: NC1=NC=NN2C1=CC=C2[C@]1(C#N)O[C@H](CO)[C@@H](O)[C@H]1O

InChiKey: BRDWIEOJOWJCLU-LTGWCKQJSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

The cells appear and grow normally at all concentrations of GS 441524 and fail to uptake the fluorescent dye CellTox Green at 24 h. The cytotoxic concentration-50% (CC50) is therefore>100 μM. The effective concentration-50% (EC50) of GS 441524 is calculated to be 0.78 μM.

In Vivo:

All 10 treated cats have a rapid response to treatment and lymphocyte levels and rectal temperatures return to pre-infection levels and levels of the two asymptomatic cats. All ten of the once or twice treated cats have remained normal to date (more than eight months post infection). Injections cause a transient "stinging" reaction in some cats within 10 s of compound administration. Localized and transient pain is evidenced by unusual posturing, licking at the injection site and/or vocalizations that last for approximately 30-60 s after injection. Injection reactions are more pronounced in some animals relative to others and reactions are inconsistent from one injection to the next and decreas over time. Remdesivi (IV injection) in NHP results in GS 441524 being present in serum at concentrations 1000-fold higher than Remdesivir throughout a 7-day treatment course.

References:

1. 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. PubMed PMID: 30755068; PubMed Central PMCID: PMC6435921.
2. 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. PubMed PMID: 29778200.

Products are for research use only. Not for human use.