| Bioactivity | 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]. |
| Invitro | MMRi62 通过诱导细胞死亡抑制胰腺导管腺癌细胞 (PDAC) 的增殖、克隆和球形生长[1]。MMRi62 (3 nM-100 μM; 4 h) 与 MDM2 和 MDM4 的环环异质二聚体结合，Kd 值为 1.39 μM[2]。MMRi62 (10 nM-1 μM; 72 h) 诱导白血病细胞凋亡，抑制白血病细胞的 IC50 分别为 0.34 μM (HL60) 和 0.22 μM (HL60VR)[2]。MMRi62 (5 μM, 10μM; 24 h) 以剂量依赖性的方式降低 MDM2B 自泛素化，增加 MDM4 泛素化[2].MMRi62 是 E3 连接酶修饰剂，能够将底物偏好从 MDM2 切换到 MDM4 [2]。MMRi62 (5 μM; 24, 72 h) 诱导细胞凋亡，不依赖于 p53[2]。 Western Blot Analysis[2] Cell Line: |
| Name | MMRi62 |
| CAS | 352693-80-2 |
| Formula | C21H15Cl2N3O |
| Molar Mass | 396.27 |
| Transport | 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) |