PF-07304814

Identification

Generic Name
PF-07304814
DrugBank Accession Number
DB16514
Background

PF-07304814 is a small molecule prodrug that targets the 3CLpro protease (Mpro), which is used by viruses like SARS-CoV-2 to assemble and multiply2. Once administered through intravenous infusion, the compound is cleaved into PF-00835231 to exert its anti-viral effects2. PF-07304814, developed by Pfizer, was first identified during the SARS outbreak in 2002-2003; it was subsequently shelved as the outbreak was controlled3. Now, it is being tested regarding the novel SARS-CoV-2 virus, including studies in conjunction with Remdesivir to treat COVID-19 infection; in vitro data showed synergistic effects on articles published on preprint servers4,1. Phase 1b studies are also exploring the safety and tolerability of PF-07304814 in COVID-19 patients who are hospitalized (NCT04535167).

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 552.521
Monoisotopic: 552.198515657
Chemical Formula
C24H33N4O9P
Synonyms
Not Available
External IDs
  • PF 07304814
  • PF-07304814
  • PF07304814

Pharmacology

Indication

Not Available

Reduce drug development failure rates
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Pharmacodynamics

Not Available

Mechanism of action

The structure of PF-07304814 contains a phosphate group, allowing the compound to be soluble and then subsequently cleaved in tissue by alkaline phosphatase2. This step allows for the release of PF-00835231, which is the compound that exerts anti-viral activity against the 3CL protease of SARS-CoV-22. The active compound, PF-00835231, was shown to have potent and broad-spectrum inhibitory activity against numerous coronavirus 3CL proteases1.

TargetActionsOrganism
AReplicase polyprotein 1ab
inhibitor
SARS-CoV-2
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
XJ51YOB1SC
CAS number
Not Available
InChI Key
FQKALOFOWPDTED-WBAXXEDZSA-N
InChI
InChI=1S/C24H33N4O9P/c1-13(2)9-18(28-24(32)19-11-15-16(26-19)5-4-6-21(15)36-3)23(31)27-17(10-14-7-8-25-22(14)30)20(29)12-37-38(33,34)35/h4-6,11,13-14,17-18,26H,7-10,12H2,1-3H3,(H,25,30)(H,27,31)(H,28,32)(H2,33,34,35)/t14-,17-,18-/m0/s1
IUPAC Name
[(3S)-3-[(2S)-2-[(4-methoxy-1H-indol-2-yl)formamido]-4-methylpentanamido]-2-oxo-4-[(3S)-2-oxopyrrolidin-3-yl]butoxy]phosphonic acid
SMILES
[H][C@@]1(C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)C2=CC3=C(N2)C=CC=C3OC)C(=O)COP(O)(O)=O)CCNC1=O

References

General References
  1. External Link [Link]
  2. c&en [Link]
  3. trial site news [Link]
  4. Comparative Study [Link]
PDBe Ligand
80I
PDB Entries
7vvp / 7wqh / 7wqi / 7wqj / 8hvu / 8hvv / 8hvw / 8hvx / 8hvy / 8hvz

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
3TerminatedTreatmentCoronavirus Disease 2019 (COVID‑19)1
1CompletedBasic ScienceHealthy Volunteers (HV)1
1CompletedTreatmentCoronavirus Disease 2019 (COVID‑19) / Viral Disease1
1CompletedTreatmentHealthy Volunteers (HV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP0.19Chemaxon
pKa (Strongest Acidic)1.21Chemaxon
pKa (Strongest Basic)-1.6Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count6Chemaxon
Polar Surface Area196.15 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity135.49 m3·mol-1Chemaxon
Polarizability54.41 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-3930250000-41b10f5b80bb23b34498
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pb9-0290330000-49fc234c0491b826c526
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-9010110000-a08872ebc9a254478ae9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052s-6960000000-661f41cd0a2174974174
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002g-6900010000-aa877803652876787db4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-020d-2910000000-b159d8e5c6f414fe2522
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
SARS-CoV-2
Pharmacological action
Yes
Actions
Inhibitor
General 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.
Specific Function
Atp binding
Gene Name
rep
Uniprot ID
P0DTD1
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
794051.285 Da

Drug created at January 21, 2021 02:02 / Updated at April 30, 2021 13:08