产品描述: | CCT007093 is an effective protein phosphatase 1D (PPM1D Wip1) inhibitor. Wip1 inhibition can activate the mTORC1 pathway and enhance hepatocyte proliferation after hepatectomy |
靶点: |
Phosphatase;Apoptosis;Autophagy;Apoptosis;Phosphatase;Autophagy |
体外研究: |
CCT007093 (25 or 50 µM, 8 h) significantly increases the phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159, and the phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) are also up-regulated in transfected HEK293T cell line. CCT007093 shows specificity for MCF-7 cells, reducing viability by 40% after 2 days with no observable effect on the growth of HeLa cells. CCT007093 induces P38 phosphorylation at 4 h post exposure in MCF-7 cells (sensitive to PPM1D inhibition), and does not induce P38 phosphorylation in HeLa cells (relatively resistant to PPM1D inhibition). Western Blot Analysis Cell Line: HEK293T cell line. Concentration: 25 or 50 µM. Incubation Time: 8 h. Result: The phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159 were all significantly increased. The phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) were also up-regulated |
体内研究: |
CCT007093 (6.4 mg/kg) enhances liver regeneration and increases the survival rate of mice following major hepatectomy. Animal Model: Wild-type mice. Dosage: 3.2 and 6.4 mg/kg. Administration: Injected intraperitoneally 4 times (mice were sacrificed at 36 h post-PH). Result: Significantly improved survival in mice following major hepatectomy (80% hepatectomy).The level of PCNA was also significantly increased in the liver of CCT007093-treated mice at 36h, 48h and 72h post-PH. |
参考文献: |
1. Lingling Zhang, et al. Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin. Hepatology. 2015 Jun;61(6):2030-41. 2. S Rayter, et al. A chemical inhibitor of PPM1D that selectively kills cells overexpressing PPM1D. Oncogene. 2008 Feb 14;27(8):1036-44. |
溶解性: |
Soluble in DMSO、DMF |
保存条件: |
-20℃ |
配置溶液浓度参考: |
|
1mg |
5mg |
10mg |
1 mM |
3.671 ml |
18.356 ml |
36.713 ml |
5 mM |
0.734 ml |
3.671 ml |
7.343 ml |
10 mM |
0.367 ml |
1.836 ml |
3.671 ml |
50 mM |
0.073 ml |
0.367 ml |
0.734 ml |
|
注意: |
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