| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T15739 | ||||
| Target Name | Cellular tumor antigenp53 | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | NUTLIN-3 | Drug Info | IC50 = 1000 nM | [530476] | |
| NU-8231 | Drug Info | IC50 = 5300 nM | [528471] | ||
| Action against Disease Model | Mepacrine | The potential role of quinacrine in enhancing the effects of cisplatin was investigated in Hela, SCC-VII, SACC-83 and C6 cancer cell lines by using a CCK-8 assay for viability and a TUNEL assay for apoptosis. quinacrine markedly enhanced the cytotoxicity of cisplatin in a dose-dependant manner in the 4 cancer cell lines. The TUNEL assay showed that treating the 4 cell lines for 24 h with cisplatin plus quinacrine significantly increased the percentage of apoptotic cells compared to treatment with single-agent treatment or untreated controls. Western blot analysis showed that quinacrine plus cisplatin significantly down-regulated cIAP-1 and up-regulated Bax and cleaved caspase-3 expression in Hela and SCC-VII cells compared with single-agent treatment. | [553043] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | A host of p53 knock-in mouse strains has been generated, with the aim of either more precisely modeling p53 mutations in h uMan cancer or better understanding p53's regulation and downstream activities.Studies of p53 mouse models have established that both p53-driven cell cycle arrest and apoptosis responses contribute to t uMor suppression and that activation of p53 by oncogenic stress imposes an important barrier to t uMorigenesis.p53 loss is not only required for t uMor development, but also t uMor maintenance,suggesting that p53 restoration in h uMan cancer patients may be a promising therapeutic strategy. | [553043] | |||
| References | |||||
| Ref 553043 | Quinacrine enhances cisplatin-induced cytotoxicity in four cancer cell lines. Chemotherapy. 2010;56(2):127-34. doi: 10.1159/000313525. Epub 2010 Apr 20. | ||||
| Ref 530476 | J Med Chem. 2009 Nov 26;52(22):7044-53.Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. | ||||
| Ref 528471 | J Med Chem. 2006 Oct 19;49(21):6209-21.Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. | ||||
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