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MedChemExpress - Model MMRi62 -352693-80-2

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].

MMRi62

MCE China：MMRi62

Brand：MedChemExpress (MCE)

Cat. No.HY-148409

CAS：352693-80-2

Purity：99.58%

Storage：4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Shipping：Room temperature in continental US; may vary elsewhere.

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.

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].

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].

References：

[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. [Content Brief]

[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. [Content Brief]

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MedChemExpress - Model MMRi62 -352693-80-2

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MMRi62