EIDD-2801

Identification

Name
EIDD-2801
Accession Number
DB15661
Type
Small Molecule
Groups
Experimental
Description

EIDD-2801 is the isopropylester prodrug of N4-hydroxycytidine.1,2 With improved oral bioavailability in non human primates, it is hydrolyzed in vivo, and distributes into tissues where it becomes the active 5’-triphosphate form.2 The active drug incorporates into the genome of RNA viruses, leading to an accumulation of mutations known as viral error catastrophe.3 Recent studies have shown EIDD-2801 inhibits replication of human and bat coronaviruses, including SARS-CoV-2, in mice and human airway epithelial cells.1 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.1

Structure
Thumb
Synonyms
Not Available
Categories
UNII
YA84KI1VEW
CAS number
2349386-89-4
Weight
Average: 329.309
Monoisotopic: 329.122299964
Chemical Formula
C13H19N3O7
InChI Key
HTNPEHXGEKVIHG-QCNRFFRDSA-N
InChI
InChI=1S/C13H19N3O7/c1-6(2)12(19)22-5-7-9(17)10(18)11(23-7)16-4-3-8(15-21)14-13(16)20/h3-4,6-7,9-11,17-18,21H,5H2,1-2H3,(H,14,15,20)/t7-,9-,10-,11-/m1/s1
IUPAC Name
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-(hydroxyimino)-2-oxo-1,2,3,4-tetrahydropyrimidin-1-yl]oxolan-2-yl]methyl 2-methylpropanoate
SMILES
CC(C)C(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=C\C(NC1=O)=N\O

Pharmacology

Indication

N4-hydroxycytidine and its prodrug EIDD-2801 is being studied for its activity against a number of viral infections including influenza, MERS-CoV, and SARS-CoV-2.1,3

Pharmacodynamics
Not Available
Mechanism of action

EIDD-2801 is hydrolyzed in vivo to N4-hydroxycytidine, which is phosphorylated in tissue to the active 5’-triphosphate form, and incorporated into the genome of new virions, resulting in the accumulation of inactivating mutations, known as viral error catastrophe.3 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.1

Absorption

EIDD-2801 is orally bioavailable in non-human primates.2

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

EIDD-2801 is hydrolyzed to N4-hydroxycytidine, which distributes into tissues.2 Once inside cells, N4-hydroxycytidine is phosphorylated to the 5'-triphosphate form.2

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Influenza Virus
  • SARS-CoV
  • SARS-CoV-2
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.
Not Available
Food Interactions
No interactions found.

References

General References
  1. T. P. Sheahan et al.: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med..
  2. Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, Plesker R, Barrena AH, Reddy PG, Mitchell DG, Shean RC, Bluemling GR, Kolykhalov AA, Greninger AL, Natchus MG, Painter GR, Plemper RK: Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med. 2019 Oct 23;11(515). pii: 11/515/eaax5866. doi: 10.1126/scitranslmed.aax5866. [PubMed:31645453]
  3. Hampton T: New Flu Antiviral Candidate May Thwart Drug Resistance. JAMA. 2020 Jan 7;323(1):17. doi: 10.1001/jama.2019.20225. [PubMed:31910262]
  4. DC Chemicals: EIDD-2081 MSDS [Link]
External Links
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentInfections, Coronavirus / Novel Coronavirus Infectious Disease (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
PropertyValueSource
Water Solubility5.77 mg/mLALOGPS
logP-1.5ALOGPS
logP-0.36ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)8.21ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area140.92 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity74.74 m3·mol-1ChemAxon
Polarizability31.66 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Drug created on April 06, 2020 20:15 / Updated on April 07, 2020 23:09

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