MMRi62

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MMRi62 是一种铁死亡 (ferroptosis) 诱导剂，靶向 MDM2-MDM4(抑癌基因 p53 负调控因子)。MMRi62 对胰腺导管腺癌 (PDAC) 细胞显示出 p53独立的促凋亡 (apoptosis) 活性，并诱导其自噬 (autophagy)。MMRi62 诱导铁死亡，伴随着活性氧增加和铁蛋白重链 (FTH1) 溶酶体降解。MMRi62 还可导致突变型 p53 的蛋白酶体降解，并对具有 KRAS 和 TP53 高频突变特征的原位异种移植 PDAC 小鼠模型具有体内药效。

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.

Western Blot Analysis 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 auto ubiquitination, increased MDM4 ubiquitination at 5 μM and 10 μM for 24 h.Induced MDM2-dependent degradation of MDM4 protein at 5 μM in NALM6 cells.Cell Proliferation Assay Cell Line:Primary AML patient cells, NALM6 cells 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.

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Apoptosis

Ferroptosis

Ferroptosis

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352693-80-2

396.27

C21H15Cl2N3O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 62.5 mg/mL (157.72 mM; 超声助溶 (<60°C)

Oc1c(ccc2cccnc12)C(Nc1ccccn1)c1cccc(Cl)c1Cl

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(-20℃)

With Ice Pack

≥ 2 years