2. Membrane Transporter/Ion Channel Anti-infection Immunology/Inflammation Apoptosis
  3. Sec61 SARS-CoV Interleukin Related TNF Receptor IFNAR
  4. 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.

For research use only. We do not sell to patients.

KZR-8445

KZR-8445 Chemical Structure

CAS No. : 2377734-91-1

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KZR-8445 Related Antibodies

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Description

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[1].

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.

KZR-8445 Related Antibodies
In Vivo

KZR-8445 (10-20 mg/kg; i.v.; thrice weekly/weekly; 2 weeks) dose-dependently blocks disease progression in a mouse model of rheumatoid arthritis[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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]
Dosage: 10 mg/kg; 20 mg/kg
Administration: i.v.; weekly/weekly; 2 weeks
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.
Molecular Weight

1083.95

Formula

C49H61BrF6N8O8
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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KZR-8445 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

KZR-84452377734-91-1KZR8445KZR 8445Sec61SARS-CoVInterleukin RelatedTNF ReceptorIFNARSec61 complex, SecY, Sec61 channel SARS coronavirusILTumor Necrosis Factor ReceptorTNFRInterferon-α/β receptorInterferon-alpha/beta receptormouse modelprimary immune cellsSec61α subunitSARS-CoV-2HEK293 Flp-In T-REx cellsrheumatoid arthritisVero E6 cellsribosome-Sec61 complexT-cell acute lymphoblastic leukemia cellshuman PBMCsInhibitorinhibitorinhibit

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