1093119-54-0
1093119-54-0 structure
- Name: MKC3946
- Chemical Name: MKC3946
- CAS Number: 1093119-54-0
- Molecular Formula: C21H20N2O3S
- Molecular Weight: 380.460
- Catalog: Signaling Pathways Cell Cycle/DNA Damage IRE1
- Create Date: 2018-01-20 11:15:43
- Modify Date: 2024-01-10 21:07:19
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MKC3946 is a potent and soluble IRE1α inhibitor, used for cancer research.
| Name | MKC3946 |
|---|---|
| Synonyms |
2-Hydroxy-6-{5-[(4-methyl-1-piperazinyl)carbonyl]-2-thienyl}-1-naphthaldehyde
1-Naphthalenecarboxaldehyde, 2-hydroxy-6-[5-[(4-methyl-1-piperazinyl)carbonyl]-2-thienyl]- MKC-3946 |
| Description | MKC3946 is a potent and soluble IRE1α inhibitor, used for cancer research. |
|---|---|
| Related Catalog | |
| 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]. |
| 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]. |
| Cell Assay | Cell proliferation and viability are examined using MTT assay. For each assay, various number of cells (1,000 for cell proliferation and 10,000 for cell viability assays) are seeded in 96-well plates, followed by either vehicle (DMSO) or increasing concentrations of drug. For detection of relative numbers of living cells, 10 μL of MTT (5 mg/mL) is added to each well, placed in an incubator for four hours, followed by centrifugation (1,000 rpm, 5 min); 100 μL of supernatant media from each well are carefullyremoved and 100 μL of SDS buffer (20% in water) is added to dissolve the crystals. Results are further read on spectrophotometer machine at 570 nM wavelength. Half maximal inhibitory concentration (IC50) is calculated using the GraphPad Prism 5. Synergy of combination of two drugs is determined using the CalcuSyn software. The extent of drug interaction between the two drugs is determined using the combination index (CI) for mutually exclusive drugs. Different CI values are obtained when solving the equation for different concentrations of drugs. A CI of 1 indicates an additive effect, whereas a CI of <1denotes synergy. All experiments are repeated at least three times. |
| Animal Admin | CB17 SCID mice (48-54 days old) are are injected subcutaneously with 1×107 RPMI 8226 cells mixed with Matrigel on day 0, and receive treatment for 21 days starting on day1. Mice are assigned into 4 groups (n=8): daily intraperitoneal injections of 100 mg/kg MKC-3946; intravenous injections of 0.15 mg/kg bortezomib twice a week; a combination of MKC-3946 intraperitoneally with bortezomib intravenously; and 10% HPBCD intraperitoneally with normal saline intravenously as a vehicle control. Tumor volume is calculated from caliper measurements every 3 to 4 days; mice are killed when tumors reach 1.5 cm in length. Survival is evaluated from the first day of treatment until death. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 591.6±50.0 °C at 760 mmHg |
| Molecular Formula | C21H20N2O3S |
| Molecular Weight | 380.460 |
| Flash Point | 311.6±30.1 °C |
| Exact Mass | 380.119476 |
| LogP | 3.17 |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.695 |
| Storage condition | -20℃ |