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Apoptosis" style="display: inline; color: #c13a36">凋亡 (Apoptosis) 活性，并诱导其Autophagy" style="display: inline; color: #c13a36">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.

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].

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].

352693-80-2

C21H15Cl2N3O

396.27

7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol

DMSO:50mg/mL (126.18mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years