GLPBio

GRL0617

Catalog No.: GC39172Purity:>99.50%
COASDSData Sheet
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.

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GRL0617
Cas No.: 1093070-16-6
10mM (in 1mL DMSO)In Stock
$64.00
1
1mgIn Stock
$27.00
1
5mgIn Stock
$58.00
1
10mgIn Stock
$93.00
1
50mgIn Stock
$280.00
1
100mgIn Stock
$402.00
1
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Description

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.

Protocol

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:
[1] 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.

Product Documents

Purity:>99.50%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
1093070-16-6
SMILES
O=C(N[C@@H](C1=C2C=CC=CC2=CC=C1)C)C3=CC(N)=CC=C3C
Molecular Formula
C20H20N2O
Molecular Weight
304.39
Solubility
DMSO: 125 mg/mL (410.66 mM)
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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