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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.
| 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 |
| Related IRE1 Products |
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BDM44768 is an inhibitior of IDE. |
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IRE1α kinase-IN-5 is a potent IRE1α inhibitor with an Ki of 98 nM. |
| Z4P
Z4P is a BBB-permeable IRE1 inhibitor (IC50: 1.11 μM). |
| IRE1α kinase-IN-9
IRE1α kinase-IN-9 is a potent IRE-1α inhibitor, exhibits an average IC50 value of <0.1 μM. |
| IRE1α kinase-IN-8
IRE1α kinase-IN-8, a benzoheterocyclecarboxaldehyde derivative, is a potent IRE-1α inhibitor. |
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