GS-441524
Identification
- Summary
GS-441524 is an experimental nucleoside analog antiviral investigated for its use in the treatment of Ebola and SARS-CoV-2 infections.
- Generic Name
- GS-441524
- DrugBank Accession Number
- DB15686
- Background
GS-441524 is an adenosine nucleotide analog antiviral, similar to remdesivir.2,5 This molecule was patented in 2009.6 In vitro studies of GS-441524 have determined it has a higher EC50 than remdesivir against a number of viruses, meaning GS-441524 is less potent.2,2 GS-441524 continues to be studied in the treatment of Feline Infectious Peritonitis Virus, a coronavirus that only infects cats.1
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for GS-441524 (DB15686)
- Weight
- Average: 291.267
Monoisotopic: 291.096753919 - Chemical Formula
- C12H13N5O4
- Synonyms
- Not Available
- External IDs
- EVO 984
- EVO-984
- EVO984
- GS-441524
- GS441524
Pharmacology
- Indication
Not Available
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Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Not Available
- Mechanism of action
GS-441524 is phosphorylated 3 times to form the active nucleoside triphosphate, which is incorporated into the genome of virions, terminating its replication.2
Target Actions Organism UReplicase polyprotein 1ab inhibitorSARS-CoV URNA-directed RNA polymerase L inhibitorZaire ebolavirus (strain Mayinga-76) - Absorption
GS-441524 has been found to transport poorly into cells compared to remdesivir.2,3,4
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
GS-441524 is phosphorylated 3 times to form the active nucleoside triphosphate.2
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAdenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with GS-441524. Anthrax vaccine The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with GS-441524. Bacillus calmette-guerin substrain connaught live antigen The therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with GS-441524. Bacillus calmette-guerin substrain russian BCG-I live antigen The therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I live antigen can be decreased when used in combination with GS-441524. Bacillus calmette-guerin substrain tice live antigen The therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with GS-441524. BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with GS-441524. Human adenovirus e serotype 4 strain cl-68578 antigen The therapeutic efficacy of Human adenovirus e serotype 4 strain cl-68578 antigen can be decreased when used in combination with GS-441524. Rubella virus vaccine The therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with GS-441524. Typhoid Vaccine Live The therapeutic efficacy of Typhoid Vaccine Live can be decreased when used in combination with GS-441524. Varicella zoster vaccine (live/attenuated) The therapeutic efficacy of Varicella zoster vaccine (live/attenuated) can be decreased when used in combination with GS-441524. 
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- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 1BQK176DT6
- CAS number
- 1191237-69-0
- InChI Key
- 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
- IUPAC Name
- (2R,3R,4S,5R)-2-{4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl}-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbonitrile
- SMILES
- NC1=NC=NN2C1=CC=C2[C@@]1(O[C@H](CO)[C@@H](O)[C@H]1O)C#N
References
- General References
- 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. [Article]
- Amirian ES, Levy JK: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health. 2020 Mar 27;9:100128. doi: 10.1016/j.onehlt.2020.100128. eCollection 2020 Jun. [Article]
- Lo MK, Jordan R, Arvey A, Sudhamsu J, Shrivastava-Ranjan P, Hotard AL, Flint M, McMullan LK, Siegel D, Clarke MO, Mackman RL, Hui HC, Perron M, Ray AS, Cihlar T, Nichol ST, Spiropoulou CF: GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep. 2017 Mar 6;7:43395. doi: 10.1038/srep43395. [Article]
- de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H: Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020 Feb 13. pii: 1922083117. doi: 10.1073/pnas.1922083117. [Article]
- FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
- European Patent Specification: 1'-substituted carba-nucleoside analogs for antiviral treatment [Link]
- External Links
- ChemSpider
- 28499294
- ChEBI
- 147281
- ChEMBL
- CHEMBL2016757
- ZINC
- ZINC000084586789
- PDBe Ligand
- U08
- Wikipedia
- GS-441524
- PDB Entries
- 7bf6
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 13.1 mg/mL ALOGPS logP -0.58 ALOGPS logP -1.9 ChemAxon logS -1.4 ALOGPS pKa (Strongest Acidic) 12.13 ChemAxon pKa (Strongest Basic) 0.65 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 8 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 149.92 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 81.95 m3·mol-1 ChemAxon Polarizability 26.99 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
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- Kind
- Protein
- Organism
- SARS-CoV
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Replicase polyprotein 1ab: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.Host transl...
- Gene Name
- rep
- Uniprot ID
- P0C6X7
- Uniprot Name
- Replicase polyprotein 1ab
- Molecular Weight
- 790241.63 Da
References
- Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR: Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: mBio.00221-18. doi: 10.1128/mBio.00221-18. [Article]
- Kind
- Protein
- Organism
- Zaire ebolavirus (strain Mayinga-76)
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their capping and polyadenylation. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor. Capping is concommitant with initiation of mRNA transcription. Indeed, a GDP polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides. Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation, both activities being carried by the viral polymerase. Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.
- Specific Function
- Atp binding
- Gene Name
- L
- Uniprot ID
- Q05318
- Uniprot Name
- RNA-directed RNA polymerase L
- Molecular Weight
- 252722.045 Da
References
- Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I: Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019 Dec 11. doi: 10.1056/NEJMoa1914510. [Article]
Drug created on May 19, 2020 16:55 / Updated on June 12, 2020 16:53