High Purity 99.5% Remdesivir Intermediate GS-441524 Powder
Product Description
Remdesivir (RDV) is the handiest US Food and Drug Administration (FDA)-permitted drug for treating COVID-19. However, RDV can handiest accept with the aid of using intravenous route, and there may be a urgent scientific want for oral antivirals. Significant proof shows that the function of the determine nucleoside GS-441524 withinside the medical consequences of RDV will be in large part underestimated. We accomplished an in vitro and in vivo drug metabolism and pharmacokinetics (DMPK) evaluation to look at the capability of RDV, and mainly GS-441524, as oral drugs. In our in vitro assessments, RDV exhibited prohibitively low balance in human liver microsomes (HLMs, t1/2 = ∼1 min), with the number one CYP-mediated metabolism being the mono-oxidation probable at the phosphoramidate moiety. This statement is poorly aligned with any capability oral use of RDV, aleven though withinside the presence of cobicistat, the microsomal balance changed into appreciably boosted to the extent discovered with out enzyme cofactor NADPH. Conversely, GS-441524 confirmed first-rate metabolic balance in human plasma and HLMs. In similarly in vivo research in CD-1 mice, GS-441524 displayed a positive oral bioavailability of 57%. Importantly, GS-441524 produced good enough drug publicity withinside the mice plasma and lung, and changed into correctly transformed to the energetic triphosphate, suggesting that it can be a promising oral antiviral drug for treating COVID-19.
| Appearance | White powder |
| GS Standard | 99.5%min |
| CAS | 1191237-69-0 |
Use and research
Since FIP is commonly deadly and there aren't anyt any permitted remedies available, GS-441524 has reportedly been offered at the black marketplace and utilized by puppy proprietors to deal with affected cats, despite the fact that Gilead Sciences has refused to license the drug for veterinary use. Its efficacy for this cause has been conclusively proven in more than one trials, together with discipline trials,or even in greater complex sorts of FIP together with people with multisystemic or neurological involvement.
Pharmacodynamics
GS-441524 nucleoside is phosphorylated with the aid of using nucleoside kinases (likely adenosine kinase (ADK), that is the enzyme that phosphorylates the structurally comparable ribavirin), after which phosphorylated once more with the aid of using nucleoside-diphosphate kinase (NDK) to the energetic nucleotide triphosphate form. The triphosphate of GS-441524, GS-443902, is likewise the bioactive anti-viral agent generated with the aid of using remdesivir, however is generated with the aid of using a extraordinary biochemical mechanism from the later.
Mechanism of action
Intracellular triple-phosphorylation of GS-441524 yields its energetic 1'-cyano-substituted adenosine triphosphate analogue, which immediately disrupts viral RNA replication with the aid of using competing with endogenous NTPs for incorporation into nascent viral RNA transcripts and triggering not on time chain termination of RNA-structured RNA polymerase.
