YL1004
YL1004 is a potent, selective and orally active noncovalent inhibitor of SARS-CoV-2 papain-like protease (PLpro). YL1004 shows an IC50 of 17.5 nM and a Ki of 2.3 nM against PLpro, with an in vitro anti-SARS-CoV-2 EC50 of 0.08 μM-1.37 μM. YL1004 suppresses the proteolytic activity of PLpro and blocks its deubiquitinating and deISGylating effects to restore host innate antiviral immune signaling. YL1004 inhibits the replication of wild-type, Delta, Omicron variants and nirmatrelvir-resistant strains of SARS-CoV-2. YL1004 can be used for the research of COVID-19 (SARS-CoV-2 infection).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Formule: C31H37N5O3
- Masse moléculaire:527.66
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
YL1004 (range; 10 min preincubation at room temperature) inhibits SARS-CoV-2 PLpro-mediated polyprotein cleavage with an IC50 of 17.5 nM and a Ki of 2.3 nM; inhibits SARS-CoV-2 PLpro-mediated deubiquitination with an IC50 of 22.9 nM and a Ki of 4.2 nM; inhibits SARS-CoV-2 PLpro-mediated deISGylation with an IC50 of 43.6 nM and a Ki of 39.3 nM[1].
YL1004 (72 h) exhibits low cytotoxicity in mammalian cell lines, with a CC50 of 226.90 μM in VeroE6 cells and 296.33 μM in Calu3 cells[1].
YL1004 directly binds to SARS-CoV-2 PLpro, as demonstrated by a ΔTm of 18.07°C in a DSF assay[1].
YL1004 (0.001-10 μM; 36 h) dose-dependently inhibits SARS-CoV-2 PLpro-mediated deubiquitination in HEK293T cells[1].
YL1004 (0.1-10 μM; co-treated with PLpro following 48 h IFN-α stimulation) dose-dependently inhibits SARS-CoV-2 PLpro-mediated deISGylation[1].
YL1004 (0.002-10 μM; co-treated with TNF-α (HY-P7058) stimulation) restores TNF-α-induced NF-κB activation in PLpro-expressing HEK293T cells with an EC50 of 44.1 nM, and restores ISRE activation with an EC50 of 265.3 nM[1].
YL1004 (0.002-10 μM; co-treated with poly (I:C) (HY-107202) stimulation) restores poly (I:C)-induced IFNB1 and IRF3 activation in PLpro-expressing HEK293T cells, with EC50 values of 26.5 nM and 206.9 nM, respectively[1].
YL1004 (18-24 h after treatment alongside poly (I:C) stimulation) restores transcription of PLpro-repressed genes involved in innate immunity, autophagy, and mitochondrial stress response in poly (I:C)-stimulated HEK293T cells[1].
YL1004 (0.039-10 μM; 22 h for wildtype/Delta/JN.1, 46 h for KP.3/NSP5-E166V) dose-dependently reduces SARS-CoV-2 sgE RNA levels in infected Calu3 cells[1].
YL1004 (48 h for wildtype/Delta, 72 h for JN.1/KP.3/NSP5-E166V post-infection) potently inhibits infectious SARS-CoV-2 replication, with EC50 values ranging from 0.08 μM to 1.37 μM across wildtype, Delta, Omicron JN.1, Omicron KP.3, and nirmatrelvir-resistant NSP5-E166V recombinant strains[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T cells
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Concentration:0.01, 0.05, 0.1, 0.25, 0.5, 1, 10 μM
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Incubation Time:36 h
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Result:Restored ubiquitinated protein levels in a dose-dependent manner.
Showed greater potency than 10 μM of a reference compound at suppressing PLPRO-mediated deubiquitination when used at 1 μM.
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Cell Line:HEK293T cells
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Concentration:0.1, 1, 10 μM
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Incubation Time:with or without IFN-α for 48 h
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Result:Reversed PLPRO-mediated reduction of ISG15-conjugated proteins in a dose-dependent manner.
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Cell Line:Calu3 cells infected with SARS-CoV-2 wildtype, Delta, Omicron JN.1, Omicron KP.3, and NSP5-E166V recombinant strains
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Concentration:0.039, 0.16, 0.63, 2.5, 110 μM
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Incubation Time:24 h (WT, Delta, JN.1); 48 h (KP.3, NSP5-E166V mutant)
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Result:Dose-dependently reduced SARS-CoV-2 sgE RNA levels; inhibited replication of WT, Delta, Omicron JN.1/KP.3 and nirmatrelvir-resistant strain.
YL1004 (100 mg/kg; p.o.; twice per day) starting 1 hour post-challenge confers 100% survival and reduces body weight loss in SARS-CoV-2 Delta-challenged K18-hACE2 mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:K18-hACE2 transgenic (8-12-week-old; male and female; intranasal inoculation with SARS-CoV-2 Omicron JN.1)[1]
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Dosage:100 mg/kg
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Administration:p.o.; twice per day
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Result:Decreased viral sgE RNA loads in nasal turbinates by 3.6-fold compared to vehicle controls.
Decreased viral sgE RNA loads in lung tissues by 26.1-fold compared to vehicle controls.
Lowered infectious viral titers in nasal turbinates by 21-fold compared to vehicle controls.
Lowered infectious viral titers in lung tissues by 13.4-fold compared to vehicle controls.
Rarely detected viral antigen in treated mouse lungs.
Significantly alleviated virus-induced pathological changes, with only mild alveolar deformation observed.
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Animal Model:K18-hACE2 transgenic (8-12-week-old; female; intranasal inoculation with SARS-CoV-2 Delta)[1]
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Dosage:100 mg/kg
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Administration:p.o.; twice per day
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Result:Reduced body weight loss significantly compared to vehicle controls.
Achieved 100% survival (10/10 mice) at 14 days post-infection, compared to 10% survival (1/10 mice) in vehicle controls.
Chemical Information
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Masse moléculaire 527.66
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Formule C31H37N5O3
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SMILES
O=C(C1=C(N)C=C2OC[C@@](CN(C)CC3)([H])N3C2=C1)NC4(C5=C6C=CC=CC6=C(NC7CCOCC7)C=C5)CC4
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
YL1004 Related Classifications
HY-181661 Related Classifications
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