raw material GS-441524

GS-441524 More Info

GS-441524 is a nucleoside analog with potent antiviral properties. It is chemically known as (2R,3S,4R,5R)-2-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile. It is the parent nucleoside of Remdesivir (GS-5734) and acts as a broad-spectrum inhibitor of viral RNA-dependent RNA polymerases (RdRp).

1. Chemical Identity

CAS Number: 1191237-69-0

Molecular Formula: C₁₂H₁₃N₅O₄

Molecular Weight: 291.26 g/mol

Structure: It is an adenosine analog. While it is the parent compound of Remdesivir, GS-441524 itself is not phosphorylated. However, it is the primary circulating metabolite of Remdesivir in vivo and is rapidly converted to the active triphosphate form (GS-443902) inside cells.

2. Mechanism of Action

GS-441524 exerts its antiviral effect by interfering with viral replication. Once inside the host cell, the compound undergoes phosphorylation to form the active triphosphate metabolite. This metabolite mimics ATP (adenosine triphosphate) and competes for incorporation into the growing viral RNA chain by the viral RdRp.

Crucially, it acts as a "chain terminator." Because of its chemical structure (specifically the nitrile group), it prevents the addition of subsequent nucleotides, thereby halting RNA synthesis. A key advantage is its ability to evade the proofreading function of the viral exoribonuclease (ExoN), making it effective against viruses that typically resist other nucleoside inhibitors.

3. Antiviral Activity

Feline Infectious Peritonitis (FIP): GS-441524 is most notably recognized for its high efficacy against Feline Infectious Peritonitis Virus (FIPV). It has demonstrated the ability to reverse clinical signs of FIP in cats, including the wet (effusive) and dry (non-effusive) forms, as well as neurological manifestations.

Coronaviruses: In vitro studies have shown activity against human coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 (COVID-19).

Other RNA Viruses: It exhibits broad-spectrum activity against a range of RNA viruses, such as Hepatitis C Virus (HCV), Yellow Fever Virus (YFV), Dengue Virus (DENV), and Influenza A.

4. Pharmacokinetics

Stability: GS-441524 shows excellent stability in human plasma and liver microsomes.

Bioavailability: It possesses favorable oral bioavailability in animal models (e.g., mice), which is a significant difference from Remdesivir, which requires intravenous administration. This allows for more flexible routes of administration in research settings.

5. Research and Development Status

Originally developed by Gilead Sciences for Ebola virus research, GS-441524 has gained significant attention in veterinary medicine for the treatment of FIP. Although it is not yet officially approved by major regulatory agencies (such as the FDA or EMA) for veterinary use, it is widely utilized in clinical research and compassionate use protocols due to its high success rate in treating this previously fatal disease in cats.