1. Cell Cycle/DNA Damage
  2. IRE1
  3. MKC3946

MKC3946 

Cat. No.: HY-19710 Purity: 99.77%
Handling Instructions

MKC3946 is a potent and soluble IRE1α inhibitor, used for cancer research.

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

MKC3946 Chemical Structure

MKC3946 Chemical Structure

CAS No. : 1093119-54-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 176 In-stock
Estimated Time of Arrival: December 31
1 mg USD 70 In-stock
Estimated Time of Arrival: December 31
5 mg USD 210 In-stock
Estimated Time of Arrival: December 31
10 mg USD 340 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1200 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1950 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 2 publication(s) in Google Scholar

Top Publications Citing Use of Products

Publications Citing Use of MCE MKC3946

    MKC3946 purchased from MCE. Usage Cited in: J Cell Mol Med. 2020 Jul 6.

    Western blotting analysis of the expression of Xbp1s, p21Cip1 and p27Kip1 in mBM‐MSCs treated with bortezomib in the presence of IRE1α inhibitor MKC3946 for 24 h. The results shows a decrease in the expression of p21Cip1 and p27Kip1.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    MKC3946 is a potent and soluble 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.

    Molecular Weight

    380.46

    Formula

    C₂₁H₂₀N₂O₃S

    CAS No.

    1093119-54-0

    SMILES

    O=CC1=C(O)C=CC2=C1C=CC(C3=CC=C(C(N4CCN(C)CC4)=O)S3)=C2

    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
    In Vitro: 

    DMSO : 20 mg/mL (52.57 mM; Need ultrasonic)

    Preparing
    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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [1]

    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 carefully removed 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.

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

    Animal Administration
    [3]

    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.

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

    References
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.
    • Molarity Calculator

    • Dilution Calculator

    The molarity calculator equation

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass   Concentration   Volume   Molecular Weight *
    = × ×

    The dilution calculator equation

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
    × = ×
    C1   V1   C2   V2

    Keywords:

    MKC3946MKC 3946MKC-3946IRE1Inositol requiring enzyme 1Inhibitorinhibitorinhibit

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

     

    Salutation

    Applicant Name *

     

    Email address *

    Phone number *

     

    Organization name *

    Department *

     

    Requested quantity *

    Country or Region *

         

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    MKC3946
    Cat. No.:
    HY-19710
    Quantity:
    MCE Japan Authorized Agent: