Background
Dorsomorphin (Compound C) is an agent that used as a cell-permeable AMPK inhibitor. It could rescue the antiproliferative actions of AICAR and metformin. Moreover, dorsomorphin (Compound C) is also used as a selective inhibitor of the BMP pathway. Compound C could inhibit a number of kinases other than AMPK.[1]
In vitro experiments indicate that Compound C inhibits AMPK activity and proliferation of human glioma cells. Dorsomorphin (Compound C) also reduces the apoptosis of cells induced by cisplatin, and decreases the expression of c-caspase3 and c-PARP in cisplatin treatment.
In vivo study demonstrate compound C attenuates cisplatin-induced nephrotoxicity in mice, and alleviates c-caspase 3 and c-PARP induced by cisplatin in kidney tissues.[1][2]
Dorsomorphin（Compound C）是一种细胞渗透的AMPK抑制剂。它可以挽救AICAR和二甲双胍的抗增殖作用。此外，dorsomorphin（Compound C）还被用作BMP通路的选择性抑制剂。 Compound C除了能够抑制AMPK之外，还能够抑制其他多种激酶。 [1]
体外实验表明，复合物C抑制AMPK活性和人脑胶质瘤细胞的增殖。Dorsomorphin（复合物C）还减少了顺铂诱导的细胞凋亡，并降低了顺铂治疗中c-caspase3和c-PARP的表达。
动物实验表明，化合物C可以减轻小鼠因顺铂引起的肾毒性，并且缓解了顺铂在肾脏组织中引起的c-caspase 3和c-PARP。[1][2]
参考文献:
[1].Liu X, et al. The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent. Mol Cancer Ther. 2014 Mar;13(3):596-605.
[2].Li F, et al. Compound C Protects Against Cisplatin-Induced Nephrotoxicity Through Pleiotropic Effects. Front Physiol. 2020 Dec 23;11:614244.
Protocol
| Cell experiment [1]: |
|
Cell lines
|
BUMPT-306
|
|
Preparation Method
|
Cells were cultured in DMEM/F12 medium containing 10% fetal bovine serum and 10% streptomycin. Then, 20 μM cisplatin was used to induce obvious apoptosis as previously indicated
|
|
Reaction Conditions
|
Cells were cultured in 20 μM of cisplatin in the presence or absence of 20 mM compound C for 24 h. To evaluate the renal tubular cells apoptosis, morphologic assay and immunoblot were used to analyze the cleaved caspase3 and PARP.
|
|
Applications
|
Dorsomorphin (Compound C) could reduce the apoptosis of cells induced by cisplatin. Moreover, compound C also decreases the expression of c-caspase3 and c-PARP in cisplatin treatment, and the protective effect of compound C was dose-dependent.
|
| Animal experiment [1]: |
|
Animal models
|
Male C57BL/6 mice (8–10 weeks)
|
|
Preparation Method
|
Mice were injected intraperitoneally with cisplatin (30 mg/kg) oncely. The control group of mice were injected with the same dose of saline. Dorsomorphin (Compound C) was dissolved in DMSO and injected intraperitoneally at 10 mg/kg 1 h before the injection of cisplatin. The no-compound C animals were administered with a comparable volume of DMSO. All the mice were euthanized at 72 h.
|
|
Dosage form
|
10 mg/kg
|
|
Applications
|
Dorsomorphin (Compound C) could reduce the severe renal tubular damage caused by cisplatin in mice. Compound C also reduces the apoptosis of renal tubular cells in mice.
|
|
参考文献:
[1]. Li F, et al. Compound C Protects Against Cisplatin-Induced Nephrotoxicity Through Pleiotropic Effects. Front Physiol. 2020 Dec 23;11:614244.
|
没有评价数据