2. Others
  3. Others
  4. M443

M443 is an irreversible and specific inhibitor of MRK, with an IC50<125 nM.

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

M443 Chemical Structure

M443 Chemical Structure

CAS No. : 1820684-31-8

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 519 In-stock
Solution
10 mM * 1 mL in DMSO USD 519 In-stock
Solid
5 mg USD 400 In-stock
10 mg USD 650 In-stock
25 mg USD 1250 In-stock
50 mg USD 1890 In-stock
100 mg USD 2950 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 2 publication(s) in Google Scholar

M443 Related Antibodies

Top Publications Citing Use of Products

2 Publications Citing Use of MCE M443

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

M443 is an irreversible and specific inhibitor of MRK, with an IC50<125 nM.

IC50 & Target

IC50: <125 nM (MRK)[1].
In Vitro

MRK depletion decreases cell viability after IR by 33% of control at 3 Gy. Similarly, the clonogenic assay shows a significant decrease in survival with a dose enhancement factor (DEF) of 1.6 at 10% viability. MRK activation by IR is maximal at 30 minutes after exposure to radiation. Therefore, for subsequent analysis, this time point is used. In both cell cultures, the IR-stimulated activation of MRK, Chk2, and p38 is greatly inhibited by 500 nM M443. Cells are seeded on coverslips, pretreated with 500 nM M443 or vehicle, exposed to 6 Gy of IR, fixed at different times after IR and processed for immunofluorescence with the MPM2 phospho-specific antibody that specifically stains mitotic cells. In contrast to control cells, the M443-treated cells fail to arrest after IR and maintained a similar mitotic index as the nonirradiated cells. Thus, inhibition of MRK leads to inhibition of Chk2 and failure to arrest in the cell cycle in response to IR-induced DNA damage[1].

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

M443 Related Antibodies
In Vivo

Control mice survive with a median of 32 days after tumor cell implantation. Treatment with M443 alone adds 5.5 days to this survival, whereas the chosen low dose of radiation does not significantly increase survival. In contrast, the combination of M443 and IR extend survival with a median of 16 days longer than control. Treatment with M443 does not affect the animal weight, as the weight loss observed is observed in all groups just a few days before the animals became moribund. It is showed that the tumor-containing fraction has elevated levels of both total and active MRK (lane RB in the vehicle-treated brain). In contrast, the tumor-containing fraction from the M443-treated brain shows total loss of MRK activity. Interestingly, the fractions containing normal brain, which in the control brain show some level of MRK protein, in the treated brain also has lost MRK, suggesting that diffusion of M443 across the whole cerebellum inhibit normal MRK as well[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

589.61

Formula

C31H30F3N7O2
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

FC(F)(F)C1=CC(NC(C2=CC(NC3=NC=CC(C4CN(C(C=C)=O)CCC4)=N3)=C(C)C=C2)=O)=CC(N5C=NC(C)=C5)=C1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 55 mg/mL (93.28 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6960 mL 8.4802 mL 16.9604 mL
5 mM 0.3392 mL 1.6960 mL 3.3921 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation

Purity: 98.95%

COA (250 KB) LCMS (102 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

Two days after transfection with siRNAs, medulloblastoma cells are seeded in a 96-well plate, and the following day, they are exposed to different doses of radiation. Cell viability is determined 72 hours after radiation treatment by MTT absorbance at 595 nm. For cells that are treated with M443 (250 nM, 500 nM), 6 hours after treatment with different concentrations of the drug or vehicle control, they are exposed to radiation and processed for the MTT assay 72 hours later as above. Five hundred cells are seeded in 6 cm dishes 2 days after siRNA transfections. The following day, cells are exposed to the different doses of radiation using a biologic irradiator and cultured for 7 days with media changes every other day. Colonies containing more than 50 cells are counted, and the results are used to calculate the surviving fractions. For the treatment with M443 or vehicle control, 24 hours after seeding, cells are exposed to the drug for 6 hours and subsequently to radiation[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
The primary UI226 medulloblastoma cells are patient derived xenografts. UI226 is largely propagated as flank cultures in nude mice and cultured in StemPro media for less than 3 weeks before intracranial injections. Medulloblastoma cells (5.0×105 UI226 in 5 mL of StemPro medium) are injected over 5 minutes into the cerebellum of 4-week-old athymic female mice. Three weeks after tumor cell implantation and approximately 2 weeks before the animals become moribund; treatment is started by implantation of an osmotic pump filled with either 0.05 mg/mL solution of M443 or vehicle (0.01% DMSO in PBS) and implanted in a subcutaneous pocket on the dorsal flank of the animal. A catheter with attached cannula delivers the drug intracranially and directly into the tumor over a period of 2 weeks, at a steady rate of 0.25 mL/hour. Irradiation of the mice head is initiated 2 days after pump implantation and conducted over 2 days[1].

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

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.6960 mL 8.4802 mL 16.9604 mL 42.4009 mL
5 mM 0.3392 mL 1.6960 mL 3.3921 mL 8.4802 mL
10 mM 0.1696 mL 0.8480 mL 1.6960 mL 4.2401 mL
15 mM 0.1131 mL 0.5653 mL 1.1307 mL 2.8267 mL
20 mM 0.0848 mL 0.4240 mL 0.8480 mL 2.1200 mL
25 mM 0.0678 mL 0.3392 mL 0.6784 mL 1.6960 mL
30 mM 0.0565 mL 0.2827 mL 0.5653 mL 1.4134 mL
40 mM 0.0424 mL 0.2120 mL 0.4240 mL 1.0600 mL
50 mM 0.0339 mL 0.1696 mL 0.3392 mL 0.8480 mL
60 mM 0.0283 mL 0.1413 mL 0.2827 mL 0.7067 mL
80 mM 0.0212 mL 0.1060 mL 0.2120 mL 0.5300 mL
  • 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.

M443 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

M4431820684-31-8M 443M-443OthersInhibitorinhibitorinhibit

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:
M443
Cat. No.:
HY-112274
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

Request for HNMR Report

We have received your request and will respond to you as soon as possible.