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MMRi62

Catalog No. T60202   CAS 352693-80-2
Synonyms: 7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol

MMRi62 (7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol), 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, CAS 352693-80-2
Pack Size Availability Price/USD Quantity
1 mg In stock $ 32.00
5 mg In stock $ 67.00
10 mg In stock $ 118.00
25 mg In stock $ 247.00
50 mg In stock $ 392.00
100 mg In stock $ 592.00
500 mg In stock $ 1,280.00
1 mL * 10 mM (in DMSO) In stock $ 75.00
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Purity: 99.7%
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Biological Description
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Description MMRi62 (7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol), 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.
In vitro MMRi62 inhibits the proliferation, cloning and spherical growth of pancreatic ductal adenocarcinoma cells (PDAC) by inducing cell death [1]. MMRi62 (3 nM-100 μ M; 4 h) Combined with the ring heterodimer of MDM2 and MDM4, Kd value is 1.39 μ M. MMRi62 (10 nM-1 μ M; 72 h) to induce apoptosis of leukemia cells, and the IC50 to inhibit leukemia cells are 0.34 respectively μ M (HL60) and 0.22 μ M (HL60VR). MMRi62 (5 μ M, 10 μ M; 24 h) Reduce the autoubiquitination of MDM2B and increase the ubiquitination of MDM4 in a dose dependent manner. MMRi62 is an E3 ligase modifier that can switch substrate preference from MDM2 to MDM4. MMRi62 (5 μ M; 24, 72 h) induced apoptosis, independent of p53 [2].
In vivo MMRi62 showed anti-tumor activity in the orthotopic xenotransplantation PDAC mouse model by inhibiting the down-regulation of NCOA4 and mutant p53 to inhibit tumor growth in mice. MMRi62 also completely eliminates metastasis of tumors in situ [1].
Synonyms 7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol
Molecular Weight 396.27
Formula C21H15Cl2N3O
CAS No. 352693-80-2

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 50mg/mL (126.18mM), sonification is recommended.

TargetMolReferences and Literature

1. Li J, et al. Small-Molecule MMRi62 Induces Ferroptosis and Inhibits Metastasis in Pancreatic Cancer via Degradation of Ferritin Heavy Chain and Mutant p53. Mol Cancer Ther. 2022 Apr 1;21(4):535-545. 2. Lama R, et al. Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status. Front Oncol. 2022 Aug 5;12:933446.

Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Compound Library Bioactive Compounds Library Max Bioactive Compound Library

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Keywords

MMRi62 352693-80-2 Apoptosis Ferroptosis 7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol inhibitor inhibit

 

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