Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition

We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2–p53 interaction. MI-219 binds to human MDM2 with a K(i) value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2–p53 interaction and activates the p53 pathway in ce...

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Detalhes bibliográficos
Main Authors: Shangary, Sanjeev, Qin, Dongguang, McEachern, Donna, Liu, Meilan, Miller, Rebecca S., Qiu, Su, Nikolovska-Coleska, Zaneta, Ding, Ke, Wang, Guoping, Chen, Jianyong, Bernard, Denzil, Zhang, Jian, Lu, Yipin, Gu, Qingyang, Shah, Rajal B., Pienta, Kenneth J., Ling, Xiaolan, Kang, Sanmao, Guo, Ming, Sun, Yi, Yang, Dajun, Wang, Shaomeng
Formato: Artigo
Idioma:Inglês
Publicado em: National Academy of Sciences 2008
Assuntos:
Biological Sciences
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC2268798/
https://ncbi.nlm.nih.gov/pubmed/18316739
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.0708917105
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