GC-376   Click here for help

GtoPdb Ligand ID: 10883

Synonyms: compound 7a [PMID: 23218713] | GC376
Compound class: Synthetic organic
Comment: GC-376 is an inhibitor of viral proteases, in particular of the 3CL protease (3CL-pro; Mpro) of coronaviruses and norovirus [4-5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 11
Hydrogen bond donors 5
Rotatable bonds 14
Topological polar surface area 179.51
Molecular weight 485.18
XLogP 0.33
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CC(C[C@@H](C(=O)N[C@H](C(S(=O)(=O)O)O)CC1CCNC1=O)NC(=O)OCc1ccccc1)C
Isomeric SMILES CC(C[C@@H](C(=O)N[C@H](C(S(=O)(=O)O)O)CC1CCNC1=O)NC(=O)OCc1ccccc1)C
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
InChI Key BSPZFJDYQHDZNR-ASPXRTSYSA-N
References
1. Dampalla CS, Kim Y, Bickmeier N, Rathnayake AD, Nguyen HN, Zheng J, Kashipathy MM, Baird MA, Battaile KP, Lovell S et al.. (2021)
Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease.
J Med Chem, 64 (14): 10047-10058. [PMID:34213885]
2. Dampalla CS, Zheng J, Perera KD, Wong LR, Meyerholz DK, Nguyen HN, Kashipathy MM, Battaile KP, Lovell S, Kim Y et al.. (2021)
Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection.
Proc Natl Acad Sci U S A, 118 (29). DOI: 10.1073/pnas.2101555118 [PMID:34210738]
3. Luttens A, Gullberg H, Abdurakhmanov E, Vo DD, Akaberi D, Talibov VO, Nekhotiaeva N, Vangeel L, De Jonghe S, Jochmans D et al.. (2022)
Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses.
J Am Chem Soc, 144 (7): 2905-2920. [PMID:35142215]
4. Ma C, Sacco MD, Hurst B, Townsend JA, Hu Y, Szeto T, Zhang X, Tarbet B, Marty MT, Chen Y et al.. (2020)
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease.
Cell Res, 30 (8): 678-692. DOI: 10.1038/s41422-020-0356-z [PMID:32541865]
5. Mandadapu SR, Gunnam MR, Tiew KC, Uy RA, Prior AM, Alliston KR, Hua DH, Kim Y, Chang KO, Groutas WC. (2013)
Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors.
Bioorg Med Chem Lett, 23 (1): 62-5. [PMID:23218713]
6. Vuong W, Khan MB, Fischer C, Arutyunova E, Lamer T, Shields J, Saffran HA, McKay RT, van Belkum MJ, Joyce MA et al.. (2020)
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.
Nat Commun, 11 (1): 4282. [PMID:32855413]
7. Xia Z, Sacco M, Hu Y, Ma C, Meng X, Zhang F, Szeto T, Xiang Y, Chen Y, Wang J. (2021)
Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir.
ACS Pharmacol Transl Sci, 4 (4): 1408-1421. [PMID:34414360]