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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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 2377734-91-1
- 分子式: C49H61BrF6N8O8
- 分子量:1083.95
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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IL-2 |
IL-1β |
IL-6 |
IL-23 |
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.
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.
化学情報
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CAS 番号 2377734-91-1
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分子量 1083.95
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
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