2. Apoptosis Autophagy
  3. Ferroptosis Apoptosis Autophagy MDM-2/p53
  4. MMRi62

MMRi62, a ferroptosis inducer targeting MDM2-MDM4 (negative regulators of tumor suppressor p53). MMRi62 shows a P53-independent pro-apoptotic activity against pancreatic ductal adenocarcinoma (PDAC) cells and induce autophagy. MMRi62 inducesferroptosis, resulting in a increase of reactive oxygen and lysosomal degradation of ferritin heavy chain (FTH1). MMRi62 also leads to proteasomal degradation of mutant p53, also inhibits orthotopic xenograft PDAC mouse model in vivo with high frequency mutation characteristics of KRAS and TP53.12.

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MMRi62 Chemical Structure

MMRi62 Chemical Structure

CAS No. : 352693-80-2

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Based on 1 publication(s) in Google Scholar

MMRi62 Related Antibodies

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Description

MMRi62, a ferroptosis inducer targeting MDM2-MDM4 (negative regulators of tumor suppressor p53). MMRi62 shows a P53-independent pro-apoptotic activity against pancreatic ductal adenocarcinoma (PDAC) cells and induce autophagy. MMRi62 inducesferroptosis, resulting in a increase of reactive oxygen and lysosomal degradation of ferritin heavy chain (FTH1). MMRi62 also leads to proteasomal degradation of mutant p53, also inhibits orthotopic xenograft PDAC mouse model in vivo with high frequency mutation characteristics of KRAS and TP53.12[1][2].

In Vitro

MMRi62 inhibits proliferation, clonogenic, and spheroid growth of pancreatic ductal adenocarcinoma cell (PDAC) by induction of cell death[1].
1 MMRi62 (3 nM-100 μM;4 h) binds to RING–RINGheterodimers of MDM2 and MDM4 withthe Kd value of 1.39 μM[2].
MMRi62 (10 nM-1 μM;72 h) induces apoptosis and inhibits leukemic cells with IC50sof 0.34 µM (HL60) and 0.22 µM (HL60VR)[2].
MMRi62 (5 μM and 10μM; 24 h) decreases MDM2B autoubiquitination, increasesMDM4 ubiquitination in a dose-dependent manner[2].
MMRi62 is an E3 ligase modifier capable ofswitching substrate preference from MDM2 to MDM4[2].
MMRi62 (5 μM; 24and 72 h) induces apoptosis in a p53-independent manner[2].

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

MMRi62 Related Antibodies

Western Blot Analysis[2]

Cell Line: WT-p53 bearing MV4-11 cells; 293cells transfected with MDM2B and MDM4
Concentration: 2, 2.5, 5, 10, 40, 80, 160 μM
Incubation Time: 24 hours
Result: Increased cleaved PARP protein and activatedcaspase 3 level in wt-p53 bearing MV4-11 cells at 2 μM for 24 h.
Decreased MDM2B autoubiquitination, increasedMDM4 ubiquitination at 5 μM and 10 μM for 24 h.
Induced MDM2-dependent degradation of MDM4protein at 5 μM in NALM6 cells.

Cell Proliferation Assay[2]

Cell Line: Primary AML patient cells, NALM6cells and NALM6shp53 cells
Concentration: 1, 10, 25, and 50 µM
Incubation Time: 24 hours and 72 hours
Result: Induced NALM6 cells apoptosis at 24 hand induced Primary AML patient cells at 72 h.
In Vivo

MMRi62 shows anti-tumor activity in orthotopic xenograft PDAC mouse models, by inhibiting tumor growth in mice associated with downregulation of NCOA4 and mutant p53[1].
MMRi62 also completely abrogates metastasis of orthotopic tumors[1].

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

396.27

Formula

C21H15Cl2N3O
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

OC1=C2N=CC=CC2=CC=C1C(C3=CC=CC(Cl)=C3Cl)NC4=NC=CC=C4
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 62.5 mg/mL (157.72 mM; ultrasonic and warming and heat to 60°C; 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 2.5235 mL 12.6177 mL 25.2353 mL
5 mM 0.5047 mL 2.5235 mL 5.0471 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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.5235 mL 12.6177 mL 25.2353 mL 63.0883 mL
5 mM 0.5047 mL 2.5235 mL 5.0471 mL 12.6177 mL
10 mM 0.2524 mL 1.2618 mL 2.5235 mL 6.3088 mL
15 mM 0.1682 mL 0.8412 mL 1.6824 mL 4.2059 mL
20 mM 0.1262 mL 0.6309 mL 1.2618 mL 3.1544 mL
25 mM 0.1009 mL 0.5047 mL 1.0094 mL 2.5235 mL
30 mM 0.0841 mL 0.4206 mL 0.8412 mL 2.1029 mL
40 mM 0.0631 mL 0.3154 mL 0.6309 mL 1.5772 mL
50 mM 0.0505 mL 0.2524 mL 0.5047 mL 1.2618 mL
60 mM 0.0421 mL 0.2103 mL 0.4206 mL 1.0515 mL
80 mM 0.0315 mL 0.1577 mL 0.3154 mL 0.7886 mL
100 mM 0.0252 mL 0.1262 mL 0.2524 mL 0.6309 mL
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MMRi62 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:

MMRi62352693-80-2MMRi 62MMRi-62FerroptosisApoptosisAutophagyMDM-2/p53Inhibitorinhibitorinhibit

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