GRL0617 |
Catalog No.GC39172
One-Click Copy Product Info
|
GRL0617 is a selective, competitive non-covalent inhibitor of severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro), with an IC₅₀ value of 0.6μM and a Kᵢ value of 0.49μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1093070-16-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
GRL0617 is a selective, competitive non-covalent inhibitor of severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro), with an IC₅₀ value of 0.6μM and a Kᵢ value of 0.49μM[1]. By inhibiting the proteolytic activity of PLpro, GRL0617 blocks the hydrolytic processing of viral polyproteins, thereby significantly reducing the replication efficiency of SARS-CoV-2. Its half-maximal effective concentration (EC₅₀) in Vero E6 cells ranges from 13.1 to 14.5μM[2]. GRL0617 effectively inhibits the deISGylating activity of PLpro, restoring the host innate immune pathway mediated by interferon-stimulated gene 15 (ISG15), thereby enhancing the cell's intrinsic immune response against viral infection[3-4].
In vitro, pretreatment of SARS-CoV-2-infected Vero E6 cells with GRL0617 (1.56–100μM) for 24–48 hours significantly reduced viral replication efficiency by inhibiting the proteolytic activity of PLpro[5]. Treatment of KYSE30 and KYSE510 esophageal squamous cell carcinoma cells with GRL0617 (5–10μM) for 24 hours reduced SLC7A11 protein expression levels by inhibiting deubiquitinase activity, significantly suppressing cell proliferation and colony formation ability, while increasing intracellular reactive oxygen species (ROS) levels[6].
References:
[1] Ratia K, Pegan S, Takayama J, et al. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16119-24.
[2] Calleja DJ, Lessene G, Komander D. Inhibitors of SARS-CoV-2 PLpro. Front Chem. 2022 Apr 26;10:876212.
[3] Cho CC, Li SG, Lalonde TJ, et al. Drug Repurposing for the SARS-CoV-2 Papain-Like Protease. ChemMedChem. 2022 Jan 5;17(1):e202100455. doi: 10.1002/cmdc.202100455. Epub 2021 Oct 12. Erratum in: ChemMedChem. 2022 Mar 4;17(5):e202200053.
[4] Shen Z, Ratia K, Cooper L, et al. Potent, Novel SARS-CoV-2 PLpro Inhibitors Block Viral Replication in Monkey and Human Cell Cultures. bioRxiv [Preprint]. 2021 Feb 15:2021.02.13.431008.
[5] Fu Z, Huang B, Tang J et al. The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery. Nat Commun. 2021 Jan 20;12(1):488.
[6] Li WT, Jin X, Song SJ, et al. Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells. Anim Cells Syst (Seoul). 2024 May 11;28(1):237-250.
| Cell experiment [1]: | |
Cell lines | Vero E6 cells (African green monkey kidney epithelial cell line) and HEK293T cells (human embryonic kidney cell line) |
Preparation Method | Vero E6 cells were cultured in DMEM supplemented with 10% FBS at 37°C, 5% CO₂. For antiviral assays, Vero E6 cells were infected with SARS-CoV-2 at MOI=0.01, and treated with GRL0617 (1.56-100μM). HEK293T cells were transfected with plasmids encoding GFP-PLpro, ISG15, E1/E2/E3 enzymes, and treated with GRL0617 (40-160μM) for ISGylation assays. |
Reaction Conditions | 1.56-100μM; 48h for antiviral assays; 40-160μM for ISGylation inhibition studies. |
Applications | GRL0617 exhibited potent antiviral activity against SARS-CoV-2 with EC₅₀=21±2μM in Vero E6 cells. GRL0617 significantly inhibited PLpro-mediated deISGylation in HEK293T cells, showing dose-dependent recovery of ISG15-conjugated cellular substrates at concentrations ≥40μM. |
References: | |
| Cas No. | 1093070-16-6 | SDF | |
| Canonical SMILES | O=C(N[C@@H](C1=C2C=CC=CC2=CC=C1)C)C3=CC(N)=CC=C3C | ||
| Formula | C20H20N2O | M.Wt | 304.39 |
| Solubility | DMSO: 125 mg/mL (410.66 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.2853 mL | 16.4263 mL | 32.8526 mL |
| 5 mM | 657.1 μL | 3.2853 mL | 6.5705 mL |
| 10 mM | 328.5 μL | 1.6426 mL | 3.2853 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)