KZR-8445
KZR-8445, a cyclic depsipeptide, is a client-selective Sec61 inhibitor. KZR-8445 binds to the fully opened Sec61 lateral gate, blocks lumenal plug domain access, stabilizes lateral gate helices, traps select signal peptides, and disrupts secretory and membrane protein biogenesis. KZR-8445 inhibits pro-inflammatory cytokine secretion in primary immune cells. KZR-8445 inhibits SARS-CoV-2 replication, virus-induced cytotoxicity, and spike protein biogenesis. KZR-8445 blocks disease progression in a mouse model of rheumatoid arthritis. KZR-8445 can be used for the researches of rheumatoid arthritis and SARS-CoV-2 infection.
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- No. CAS: 2377734-91-1
- Fòrmula: C49H61BrF6N8O8
- Peso molecular:1083.95
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
IL-2 |
IL-1β |
IL-6 |
IL-23 |
In Vitro
KZR-8445 (0.1-10000 nM; 24 h) directly targets Sec61α to potently inhibit secretion of IL-2-GLuc and TNFα-GLuc in HEK293 Flp-In T-REx cells expressing WT Sec61α, with an IC50 of ~100 nM[1].
KZR-8445 (24 h) inhibits secretion of GLuc reporters fused to HER3, prolactin, PD1, TNFα, and IL-2 signal peptides in HEK293 Flp-In T-REx cells with IC50 values ranging from 32 nM to 1068 nM[1].
KZR-8445 potently inhibits secretion of Sec61-dependent pro-inflammatory cytokines with submicromolar IC50 values in activated human PBMCs, while sparing cell viability at concentrations up to 20 µM[1].
KZR-8445 (0.01-10 µM; 2 h) inhibits SARS-CoV-2 replication and spike protein biogenesis in Vero E6 cells while maintaining cell viability above 50% at concentrations up to 10 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 7-8 weeks old, rheumatoid arthritis induced via intravenous anti-type II collagen antibody cocktail on day 0 + intraperitoneal LPS (HY-D1056) on day 3)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.v.; weekly/weekly; 2 weeks
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Result:Blocked disease progression with a statistically significant effect at 10 and 20 mg/kg thrice weekly.
Significantly blocked disease progression at 20 mg/kg weekly.
Showed no significant toxicity, with body weight changes comparable to or greater than vehicle-treated mice across all treatment groups.
- Collagen-Induced Arthritis
- Research Protocol for Infectious Diseases
- Cell Cytotoxicity Assay
- Mammalian live/dead viability and cytotoxicity staining
- Membrane Protein Extraction Using Detergents and Chaotropes
- Research Protocol for Inflammation-related Diseases
- Cell Viability Determination by MTT Colorimetric Assay
- How to Choose the Right Model Animal
Chemical Information
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No. CAS 2377734-91-1
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Peso molecular 1083.95
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Fòrmula C49H61BrF6N8O8
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SMILES
BrC(C=C1)=CC=C1CN2C3=CC=CC=C3C(C[C@@H]4N(C([C@@H](NC([C@@H](N(C([C@@H](NC([C@H](OC([C@@H](N(C([C@@H](NC4=O)CC(C)C)=O)C)C)=O)CCC#N)=O)CC(F)(F)F)=O)C)CC(C)C)=O)CC(F)(F)F)=O)C)=C2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KZR-8445 Related Classifications
HY-P10466 Related Classifications
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