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

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

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

Sanjeev Shangary,Dongguang Qin,Donna McEachern,Meilan Liu,Rebecca S Miller,Su Qiu,Zaneta Nikolovska-Coleska,Ke Ding,Guoping Wang,Jianyong Chen,Denzil Bernard,Jian Zhang,Yipin Lu,Qingyang Gu,Rajal B Shah,Kenneth J Pienta,Xiaolan Ling,Sanmao Kang,Ming Guo,Yi Sun,Dajun Yang,Shaomeng Wang,

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 cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment.

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

S Shangary,D Qin,D McEachern,M Liu,RS Miller,S Qiu,Z Nikolovska-Coleska,K Ding,G Wang,J Chen,D Bernard,J Zhang,Y Lu,Q Gu,RB Shah,KJ Pienta,X Ling,S Kang,M Guo,Y Sun,D Yang,S Wang,

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 3933-8

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ISSN: 1091-6490

DAY: 3

MONTH: 03

YEAR: 2008

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

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LANGUAGE: eng

NlmUniqueID: 7505876

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

AFFILIATION: Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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