352693-80-2
352693-80-2 structure
- Name: MMRi62
- Chemical Name: MMRi62
- CAS Number: 352693-80-2
- Molecular Formula: C21H15Cl2N3O
- Molecular Weight: 396.27
- Catalog: Signaling Pathways Apoptosis Apoptosis
- Create Date: 2023-01-15 19:45:26
- Modify Date: 2024-04-06 11:33:51
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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].
| Name | MMRi62 |
|---|---|
| Synonyms | MFCD01647927 |
| 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[1][2]. |
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| Related Catalog | |
| In Vitro | 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: 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 autoubiquitination, increasedMDM4 ubiquitination at 5 μM and 10 μM for 24 h. Induced MDM2-dependent degradation of MDM4protein at 5 μM in NALM6 cells. Cell Proliferation Assay[2] Cell Line: Primary AML patient cells, NALM6cells 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. |
| In Vivo | MMRi62 在原位异种移植 PDAC 小鼠模型中显示出抗肿瘤活性，通过抑制 NCOA4 和突变型 p53 下调，抑制小鼠的肿瘤生长[1]。 MMRi62 也完全消除原位肿瘤的转移[1]。 |
| References |
| Molecular Formula | C21H15Cl2N3O |
|---|---|
| Molecular Weight | 396.27 |