| 产品描述： | Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC50 of 0.6 nM. Navtemadlin binds to MDM2 with a Kd of 0.045 nM |
| 靶点： |
IC50: 0.6 nM (p53-MDM2 interaction) Kd: 0.045 nM (MDM2);Mdm2; E1/E2/E3Enzyme |
| 体外研究： |
Navtemadlin (AMG 232) (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines. Navtemadlin potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells (IC50=10 nM). Cell Viability Assay Cell Line: SJSA-1, HCT116, ACHN, NCI-H460, MOLM-13, RKO, MCF7, 22RV1, HT-29, PC-3, NCI-H82, NCI-SNU1, MG-63, NCI-H2452, SW982, C32, SK-HEP-1, A375, RT4, RPMI2650, MDA-MB-134-VI, NCI-H2347 and A427 cells.Concentration: 0-10 μM. Incubation Time: 72 hours. Result: Induced p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN).Caused robust p21 mRNA induction between 9.76 and 34.9 fold with IC50 values ranging from 12.8 to 46.8 nM. |
| 体内研究： |
Navtemadlin (AMG 232) (10, 25, 75 mg/kg, once daily, p.o.) activates p53 pathway activity in vivo. Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) potently inhibits growth of tumor xenografts in mice. Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) blocks DNA synthesis and induces apoptosis in vivo. Navtemadlin causes a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg. Animal Model: Female athymic nude mice (n=10/group) based cancer models. Dosage: 10, 25, 75 mg/kg. Administration: Once daily by oral gavage. Result: Resulted in significant tumor growth inhibition across all models. SJSA-1, an MDM2 amplified osteosarcoma model, was the most sensitive to AMG 232 treatment with an ED50 of 9.1 mg/kg. In the highest dose group of 75 mg/kg, 10/10 tumors completely regressed and were undetectable after 10 days of treatment. |
| 参考文献： |
1. Canon J, et al. The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents. Mol Cancer Ther. 2015 Mar;14(3):649-58. 2. Rew Y, et al. Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41. |
| 溶解性： |
Soluble in DMSO、H2O |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.759 ml |
8.794 ml |
17.589 ml |
| 5 mM |
0.352 ml |
1.759 ml |
3.518 ml |
| 10 mM |
0.176 ml |
0.879 ml |
1.759 ml |
| 50 mM |
0.035 ml |
0.176 ml |
0.352 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京