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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2D Structure
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Physico-chemical Properties
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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
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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
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, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.1c00319 [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, [Epub ahead of print]. DOI: 10.1021/jacs.1c08402 [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]