Synonym
GC376; GC-376; GC 376; GC376 sodium.
IUPAC/Chemical Name
sodium (2S)-2-((S)-2-(((benzyloxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate
InChi Key
BSPJDKCMFIPBAW-JPBGFCRCSA-M
InChi Code
InChI=1S/C21H31N3O8S.Na/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);/q;+1/p-1/t15?,16-,17-,20?;/m0./s1
SMILES Code
O=S(C(O)[C@@H](NC([C@@H](NC(OCC1=CC=CC=C1)=O)CC(C)C)=O)CC2C(NCC2)=O)([O-])=O.[Na+]
Purity
>96% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO and water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GC376 inhibits the replication of viruses TGEV, FIPV and PTV with IC50 values of 0.15, 0.2 and 0.15 μM,
respectively.
In vitro activity:
Boceprevir and GC376 both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting Mpro. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease Mpro as main mechanism of inhibition.
Reference: Nat Commun. 2020 Sep 4;11(1):4417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474075/
In vivo activity:
Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 105 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 103 TCID50/mouse.
Reference: Sci Rep. 2021 May 5;11(1):9609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100161/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
55.0 |
108.37 |
| DMF |
10.0 |
19.70 |
| PBS |
10.0 |
19.70 |
| Water |
100.0 |
197.03 |
| Ethanol |
2.0 |
3.94 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
507.53
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Fu L, Ye F, Feng Y, Yu F, Wang Q, Wu Y, Zhao C, Sun H, Huang B, Niu P, Song H, Shi Y, Li X, Tan W, Qi J, Gao GF. Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nat Commun. 2020 Sep 4;11(1):4417. doi: 10.1038/s41467-020-18233-x. PMID: 32887884; PMCID: PMC7474075.
2. Cáceres CJ, Cardenas-Garcia S, Carnaccini S, Seibert B, Rajao DS, Wang J, Perez DR. Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model. Sci Rep. 2021 May 5;11(1):9609. doi: 10.1038/s41598-021-89013-w. PMID: 33953295; PMCID: PMC8100161.
In vitro protocol:
1. Fu L, Ye F, Feng Y, Yu F, Wang Q, Wu Y, Zhao C, Sun H, Huang B, Niu P, Song H, Shi Y, Li X, Tan W, Qi J, Gao GF. Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nat Commun. 2020 Sep 4;11(1):4417. doi: 10.1038/s41467-020-18233-x. PMID: 32887884; PMCID: PMC7474075.
In vivo protocol:
1. Cáceres CJ, Cardenas-Garcia S, Carnaccini S, Seibert B, Rajao DS, Wang J, Perez DR. Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model. Sci Rep. 2021 May 5;11(1):9609. doi: 10.1038/s41598-021-89013-w. PMID: 33953295; PMCID: PMC8100161.
1: 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. PMID: 28901812; PMCID: PMC5871025.
2: Fumian TM, Tuipulotu DE, Netzler NE, Lun JH, Russo AG, Yan GJH, White PA. Potential Therapeutic Agents for Feline Calicivirus Infection. Viruses. 2018 Aug 16;10(8):433. doi: 10.3390/v10080433. PMID: 30115859; PMCID: PMC6116245.
3: Perera KD, Rathnayake AD, Liu H, Pedersen NC, Groutas WC, Chang KO, Kim Y. Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor. Vet Microbiol. 2019 Oct;237:108398. doi: 10.1016/j.vetmic.2019.108398. Epub 2019 Aug 23. PMID: 31585653; PMCID: PMC6779346.
4: Takahashi D, Kim Y, Lovell S, Prakash O, Groutas WC, Chang KO. Structural and inhibitor studies of norovirus 3C-like proteases. Virus Res. 2013 Dec 26;178(2):437-44. doi: 10.1016/j.virusres.2013.09.008. Epub 2013 Sep 17. PMID: 24055466; PMCID: PMC3840063.
5: Kim Y, Lovell S, Tiew KC, Mandadapu SR, Alliston KR, Battaile KP, Groutas WC, Chang KO. Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses. J Virol. 2012 Nov;86(21):11754-62. doi: 10.1128/JVI.01348-12. Epub 2012 Aug 22. PMID: 22915796; PMCID: PMC3486288.
