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MKC-3946

Cat. No. M10395
MKC-3946 Structure
Synonym:

MKC3946

Size Price Availability Quantity
1mg USD 70  USD70 In stock
5mg USD 200  USD200 In stock
10mg USD 320  USD320 In stock
25mg USD 680  USD680 In stock
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Quality Control & Documentation
Biological Activity

MKC-3946 is a potent IRE1α inhibitor which triggered modest growth inhibition in multiple myeloma cell lines. MKC-3946 blocks XBP1 mRNA splicing and exhibit cytotoxicity against AML cells. MKC-3946 inhibits XBP1S expression induced by tunicamycin (TM) in NB4 cells (B) and AML. MKC-3946 prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production. MKC-3946 (10μM) enhances ER stress-mediated apoptosis induced by bortezomib or 17-AAG, and enhances cytotoxicity of ER stressors, even in the presence of BMSCs or exogenous IL-6.

In vivo, MKC-3946 (100 mg/kg, i.p.) inhibits XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells, alone or with bortezomib. MKC-3946 significantly reduces MM tumor growth in the treatment versus control group.

Chemical Information
Molecular Weight 380.46
Formula C21H20N2O3S
CAS Number 1093119-54-0
Solubility (25°C) DMSO 20 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Aurelia Lugea, et al. Gastroenterology. The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells

[2] Haibo Sun, et al. Oncotarget. Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia

[3] Liling Zhang, et al. BMC Cell Biol. IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis

[4] Naoya Mimura, et al. Blood. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma

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  Catalog
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Keywords: MKC-3946, MKC3946 supplier, IRE1, inhibitors, activators


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