NAV

GC-376

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
GC-376 free acid
Commonly known or available as GC-376
DrugBank Accession Number
DB15796
Background

GC-376 is a 3C-like protease (3CLpro or Mpro) inhibitor that stops the cleavage and activation of functional viral proteins required for replication and transcription in host cells1. The compound is known as a direct acting antiviral (DAA) for coronaviruses, and was initially developed using structure-guided design to combat MERS-Cov infections1,2. In addition, GC-376 displays potent activity against various coronaviruses such as feline, ferret, and mink Mpro coronavirus3,4,1,5. A prodrug of GC-373, GC-376 has recently been used to test inhibition of SARS-Cov-2 Mpro in vitro, and results show potent inhibition of this target1. These results suggest that GC-376, and its metabolites may have therapeutic potential for Covid-19.

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 485.55
Monoisotopic: 485.183186144
Chemical Formula
C21H31N3O8S
Synonyms
Not Available
External IDs
  • GC-376 free acid
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Pharmacology

Indication

Not Available

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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UReplicase polyprotein 1ab
inhibitor
SARS-CoV-2
UReplicase polyprotein 1a
inhibitor
SARS-CoV-2
UReplicase polyprotein 1ab
inhibitor
Feline coronavirus (strain FIPV WSU-79/1146)
UReplicase polyprotein 1aNot AvailableMiddle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
UReplicase polyprotein 1abNot AvailableMiddle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
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

Products

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Product Ingredients
IngredientUNIICASInChI Key
GC-376H1NMJ5XDG51416992-39-6BSPJDKCMFIPBAW-JPBGFCRCSA-M

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
O9H5KY11SV
CAS number
1417031-79-8
InChI Key
BSPZFJDYQHDZNR-ASPXRTSYSA-N
InChI
InChI=1S/C21H31N3O8S/c1-13(2)10-16(24-21(28)32-12-14-6-4-3-5-7-14)19(26)23-17(20(27)33(29,30)31)11-15-8-9-22-18(15)25/h3-7,13,15-17,20,27H,8-12H2,1-2H3,(H,22,25)(H,23,26)(H,24,28)(H,29,30,31)/t15?,16-,17-,20?/m0/s1
IUPAC Name
(2S)-2-[(2S)-2-{[(benzyloxy)carbonyl]amino}-4-methylpentanamido]-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonic acid
SMILES
CC(C)C[C@H](NC(=O)OCC1=CC=CC=C1)C(=O)N[C@@H](CC1CCNC1=O)C(O)S(O)(=O)=O

References

General References
  1. Vuong W, Khan MB, Fischer C, Arutyunova E, Lamer T, Shields J, Saffran HA, McKay RT, van Belkum MJ, Joyce MA, Young HS, Tyrrell DL, Vederas JC, Lemieux MJ: Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun. 2020 Aug 27;11(1):4282. doi: 10.1038/s41467-020-18096-2. [Article]
  2. Galasiti Kankanamalage AC, Kim Y, Damalanka VC, Rathnayake AD, Fehr AR, Mehzabeen N, Battaile KP, Lovell S, Lushington GH, Perlman S, Chang KO, Groutas WC: Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element. Eur J Med Chem. 2018 Apr 25;150:334-346. doi: 10.1016/j.ejmech.2018.03.004. Epub 2018 Mar 6. [Article]
  3. Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO: Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J Feline Med Surg. 2018 Apr;20(4):378-392. doi: 10.1177/1098612X17729626. Epub 2017 Sep 13. [Article]
  4. Kim Y, Shivanna V, Narayanan S, Prior AM, Weerasekara S, Hua DH, Kankanamalage AC, Groutas WC, Chang KO: Broad-spectrum inhibitors against 3C-like proteases of feline coronaviruses and feline caliciviruses. J Virol. 2015 May;89(9):4942-50. doi: 10.1128/JVI.03688-14. Epub 2015 Feb 18. [Article]
  5. Perera KD, Galasiti Kankanamalage AC, Rathnayake AD, Honeyfield A, Groutas W, Chang KO, Kim Y: Protease inhibitors broadly effective against feline, ferret and mink coronaviruses. Antiviral Res. 2018 Dec;160:79-86. doi: 10.1016/j.antiviral.2018.10.015. Epub 2018 Oct 19. [Article]
ChemSpider
29399539
ChEMBL
CHEMBL2365410

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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
Water Solubility1.79 mg/mLALOGPS
logP-0.41ALOGPS
logP-0.55Chemaxon
logS-2.4ALOGPS
pKa (Strongest Acidic)-0.88Chemaxon
pKa (Strongest Basic)-1.5Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area171.13 Å2Chemaxon
Rotatable Bond Count12Chemaxon
Refractivity117.4 m3·mol-1Chemaxon
Polarizability48.62 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000f-7229200000-7125a68a8a4cc40af730
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-1091000000-9065b67fefac1e892945
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9834200000-1ddeeef6b074cafe52a6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-1259000000-3598d3db4c5b55bfb58d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9502100000-0647851712ac194fe10e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0c0u-7933000000-9ec18330b8e5fa6867a1
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Replicase polyprotein 1ab
Kind
Protein
Organism
SARS-CoV-2
Pharmacological action
Unknown
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
Details2. Replicase polyprotein 1a
Kind
Protein
Organism
SARS-CoV-2
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Replicase polyprotein 1a Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.
Specific Function
Cysteine-type endopeptidase activity
Gene Name
Not Available
Uniprot ID
P0DTC1
Uniprot Name
Replicase polyprotein 1a
Molecular Weight
489984.88 Da
Details3. Replicase polyprotein 1ab
Kind
Protein
Organism
Feline coronavirus (strain FIPV WSU-79/1146)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
Specific Function
Atp binding
Gene Name
rep
Uniprot ID
Q98VG9
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
751190.21 Da
Details4. Replicase polyprotein 1a
Kind
Protein
Organism
Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Pharmacological action
Unknown
General Function
The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
Specific Function
Cysteine-type endopeptidase activity
Gene Name
Not Available
Uniprot ID
K9N638
Uniprot Name
Replicase polyprotein 1a
Molecular Weight
486054.32 Da
Details5. Replicase polyprotein 1ab
Kind
Protein
Organism
Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Pharmacological action
Unknown
General Function
The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
Specific Function
Atp binding
Gene Name
rep
Uniprot ID
K9N7C7
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
789556.615 Da

Drug created at September 03, 2020 15:32 / Updated at September 03, 2020 20:56