1911579-04-8

Basic information

• Product Name: GS-704277
• CAS NO: 1911579-04-8
• Molecular Weight: 442.325
• Mol File: 1911579-04-8.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: GS-704277(CAS DataBase Reference)
• NIST Chemistry Reference: GS-704277(1911579-04-8)
• EPA Substance Registry System: GS-704277(1911579-04-8)

Safety Data

• Hazardous Substances Data: 1911579-04-8(Hazardous Substances Data)

Usage

Description

GS-704277, also known as Dephenoxy Hydroxy Remdesivir, is an impurity of Remdesivir (CAS#: 1809249-37-3). It is a small molecule with therapeutic efficacy against the Ebola virus, particularly in rhesus monkeys. GS-704277 has gained attention for its potential applications in the medical field due to its antiviral properties.

Uses

Used in Antiviral Applications:
GS-704277 is used as an antiviral agent for the treatment of Ebola virus infections in rhesus monkeys. Its therapeutic efficacy has been demonstrated in preclinical studies, making it a promising candidate for further research and development in the field of antiviral drug discovery.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, GS-704277 is used as a reference compound for the development of new antiviral drugs. Its structure and activity against the Ebola virus can provide valuable insights for the design and synthesis of novel therapeutic agents targeting similar viral pathogens.
Used in Research and Development:
GS-704277 is used as a research tool for understanding the mechanisms of action and resistance development in viral infections. Its study can contribute to the advancement of knowledge in virology and the development of more effective antiviral strategies.
It is important to note that the information provided is based on the limited data available and may not cover all potential applications of GS-704277. Further research and development are necessary to fully understand its potential and limitations in various fields.

Upstream product

• 1809249-37-3 (2S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate 

Relevant articles and documents

Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.