GC-373

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

Identification

Generic Name

GC-373

DrugBank Accession Number

DB15797

Background

GC-373 is a peptide aldehyde which is metabolized from the bisulfide adduct, GC-376 free acid^1,2. It is an inhibitor of M^pro (otherwise known as 3CL^pro), a viral encoded protease that cleaves and activates functional proteins involved in viral replication and transcription². GC-373 has been shown to inhibit the M^pro target in various coronavirus strains, including feline, mink, and ferret M^pro ³. Along with its prodrug, GC-376, GC-373 was recently investigated in vitro in cell culture against SARS-Cov-2 M^pro ². The results showed potent inhibition of the target, suggesting that GC-373 holds therapeutic potential for Covid-19².

Type

Small Molecule

Groups

Experimental

Structure

Similar Structures

Weight: Average: 403.479
Monoisotopic: 403.210721046
Chemical Formula: C₂₁H₂₉N₃O₅

Synonyms

Not Available

External IDs

GC-373
GC373

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings

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Pharmacodynamics

Not Available

Mechanism of action

Target	Actions	Organism
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)
AReplicase polyprotein 1ab	inhibitor	Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
AReplicase polyprotein 1a	inhibitor	Middle 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

Chemical Identifiers

UNII: Not Available
CAS number: Not Available
InChI Key: QYENXTYKACLCGO-FQECFTEESA-N
InChI: InChI=1S/C21H29N3O5/c1-14(2)10-18(24-21(28)29-13-15-6-4-3-5-7-15)20(27)23-17(12-25)11-16-8-9-22-19(16)26/h3-7,12,14,16-18H,8-11,13H2,1-2H3,(H,22,26)(H,23,27)(H,24,28)/t16?,17-,18-/m0/s1
IUPAC Name: benzyl N-[(1S)-3-methyl-1-{[(2S)-1-oxo-3-(2-oxopyrrolidin-3-yl)propan-2-yl]carbamoyl}butyl]carbamate
SMILES: CC(C)C[C@H](NC(=O)OCC1=CC=CC=C1)C(=O)N[C@@H](CC1CCNC1=O)C=O

References

General References

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]
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]
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]

External Links

ChemSpider: 26617691
ChEMBL: CHEMBL1821850

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

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

Property	Value	Source
Water Solubility	0.0386 mg/mL	ALOGPS
logP	1.04	ALOGPS
logP	1.28	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	12.68	ChemAxon
pKa (Strongest Basic)	-1.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	113.6 Å²	ChemAxon
Rotatable Bond Count	11	ChemAxon
Refractivity	106.58 m³·mol^-1	ChemAxon
Polarizability	42.97 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	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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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 1ab

Kind: Protein
Organism: Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Pharmacological action: Yes
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: K9N7C7
Uniprot Name: Replicase polyprotein 1ab
Molecular Weight: 789556.615 Da

Details5. Replicase polyprotein 1a

Kind: Protein
Organism: Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Pharmacological action: Yes
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: Cysteine-type endopeptidase activity
Gene Name: Not Available
Uniprot ID: K9N638
Uniprot Name: Replicase polyprotein 1a
Molecular Weight: 486054.32 Da

Drug created on September 03, 2020 15:38 / Updated on September 03, 2020 20:54

GC-373

Identification

Structure for GC-373 (DB15797)

Pharmacology

Interactions

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets