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

Biological activity of GS-441524

Description GS-441524 has a strong inhibitory effect on feline infectious peritonitis virus (FIPV) with an EC50 value of 0.78 μM.

Related category

Research Field > > infection

Signal path > > Cell cycle /DNA damage > > DNA/RNA synthesis

target

EC50: 0.78μM (FIPV)[1].

Cells studied in vitro appeared and grew normally at all concentrations of GS-441524 and failed to take up the fluorescent dye CellTox Green within 24 h. Therefore, the cytotoxic concentration of -50% (CC50) is greater than 100μM. The effective concentration of GS-441524 -50% (EC50) was calculated as 0.78μM[1].

In vivo studies All 10 cats treated responded quickly to treatment, with lymphocyte levels and rectal temperature returning to pre-infection levels and those of two asymptomatic cats. Of the 10 treated cats, 16-116 (group A) and 16-127 (group B) developed recurrent disease at 4 and 6 weeks after treatment. Both cats received the second treatment for two weeks, and they responded in the same way as the first treatment. To date, all 10 cats treated once or twice remained normal (more than eight months after infection). Some cat injections cause a brief "tingling" reaction within 10 seconds of administration. Local and transient pain is manifested by unusual posture, licking at the injection site, and/or vocalization lasting approximately 30-60 seconds after injection. The injection response is more pronounced in some animals than others, and the response is inconsistent from one injection to another and diminishes over time [1].

Cell assay To determine the toxicity of GS-441524 to CRFK cell n, CRFK cells were treated with 100, 33.3, 11.1, 3.7, or 1.2μM of GS-441524 for 24 h [1].

Animal laboratory cats [1] Ten cats with signs of disease were divided into two groups and given 5 mg/kg (group A; n=5) or 2 mg/kg (Group B; n=5) GS-441524 SC q24h treatment. Two cats with no symptoms of disease were used as controls for normal blood lymphocyte counts and rectal temperature [1].

Reference literature

[1]. Murphy BG, et al. 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.

GS-441524 Physical and Chemical properties

Density 1.84± 0.1g

Molecular formula C12H13N5O4

Molecular weight 291.26

Accurate mass 291.0968

Appearance characteristics Solid powder

Storage conditions Dry, dark and at 0-4 C for short term (days to weeks) or -20 C for long term (months to years).

Water Soluble in DMSO

GS-441524 Alias in English

2 - C - (4 - Aminopyrrolo [2, 1 - f] [1, 2, 4] triazin - 7 - yl) - 2, 5 - anhydro - D - altrononitrile

Remdesivir metabolite