[CAS NO. 1093119-54-0] MKC3946
PRODUCTS SPECIFICATIONS [1093119-54-0]
DESCRIPTION [1093119-54-0]
Overview
| MDL | MFCD30496700 |
|---|---|
| Molecular Weight | 380.46 |
| Molecular Formula | C21H20N2O3S |
| SMILES | O=CC1=C(O)C=CC2=C1C=CC(C3=CC=C(C(N4CCN(C)CC4)=O)S3)=C2 |
4 Publications Citing Use of MCE
Summary
MKC3946 is a potent IRE1α inhibitor, used for cancer research.
In Vitro
MKC-3946 blocks XBP1 mRNA splicing and exhibits cytotoxicity against AML cells. MKC-3946 inhibits XBP1S expression induced by tunicamycin (TM) in NB4 cells (B) and AML sample from patients [1] . MKC-3946 prevents the splicing of the XBP1 mRNA in response to ER stress caused by mutant proinsulin production [2] . MKC-3946 is an IRE1α endoribonuclease domain inhibitor that blocks XBP1 mRNA splicing and triggers modest growth inhibition in MM cells. MKC-3946 inhibits XBP1s expression induced by Tm in a dose-dependent manner, but does not affect phosphorylation of IRE1α. MKC-3946 blocks XBP1 splicing and enhances cytotoxicity induced by bortezomib or 17-AAG. 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 [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. Inhibition of XBP1 splicing by MKC-3946 is associated with decreased MM growth in vivo, alone or in combination with bortezomib [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 20 mg/mL ( 52.57 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6284 mL | 13.1420 mL | 26.2840 mL |
| 5 mM | 0.5257 mL | 2.6284 mL | 5.2568 mL |
| 10 mM | 0.2628 mL | 1.3142 mL | 2.6284 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2 mg/mL (5.26 mM); Clear solution
References
- [1] Sun H, et al. Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia. Oncotarget. 2016 Apr 5;7(14):18736-49
- [2] Zhang L, et al. IRE1 inhibition perturbs the unfolded protein response in a pancreatic β-cell line expressing mutant proinsulin, but does not sensitize the cells to apoptosis. BMC Cell Biol. 2014 Jul 10;15:29.
- [3] Mimura N, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood. 2012 Jun 14;119(24):5772-81