Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction

Shanghai Yu, Dongguang Qin, Sanjeev Shangary, Jianyong Chen, Guoping Wang, Ke Ding, Donna McEachern, Su Qiu, Zaneta Nikolovska-Coleska, Rebecca Miller, Sanmao Kang, Da-Jun Yang, Shaomeng Wang

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Compound 5 binds to MDM2 with a K i of 0.6 nM, activates p53 at concentrations as low as 40 nM, and potently and selectively inhibits cell growth in tumor cells with wild-type p53 over tumor cells with mutated/deleted p53. Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model.

Original languageEnglish (US)
Pages (from-to)7970-7973
Number of pages4
JournalJournal of Medicinal Chemistry
Volume52
Issue number24
DOIs
StatePublished - Dec 24 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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Yu, S., Qin, D., Shangary, S., Chen, J., Wang, G., Ding, K., ... Wang, S. (2009). Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Journal of Medicinal Chemistry, 52(24), 7970-7973. https://doi.org/10.1021/jm901400z

Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. / Yu, Shanghai; Qin, Dongguang; Shangary, Sanjeev; Chen, Jianyong; Wang, Guoping; Ding, Ke; McEachern, Donna; Qiu, Su; Nikolovska-Coleska, Zaneta; Miller, Rebecca; Kang, Sanmao; Yang, Da-Jun; Wang, Shaomeng.

In: Journal of Medicinal Chemistry, Vol. 52, No. 24, 24.12.2009, p. 7970-7973.

Research output: Contribution to journalArticle

Yu, S, Qin, D, Shangary, S, Chen, J, Wang, G, Ding, K, McEachern, D, Qiu, S, Nikolovska-Coleska, Z, Miller, R, Kang, S, Yang, D-J & Wang, S 2009, 'Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction', Journal of Medicinal Chemistry, vol. 52, no. 24, pp. 7970-7973. https://doi.org/10.1021/jm901400z
Yu, Shanghai ; Qin, Dongguang ; Shangary, Sanjeev ; Chen, Jianyong ; Wang, Guoping ; Ding, Ke ; McEachern, Donna ; Qiu, Su ; Nikolovska-Coleska, Zaneta ; Miller, Rebecca ; Kang, Sanmao ; Yang, Da-Jun ; Wang, Shaomeng. / Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 24. pp. 7970-7973.
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AU - Qin, Dongguang

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AU - Wang, Guoping

AU - Ding, Ke

AU - McEachern, Donna

AU - Qiu, Su

AU - Nikolovska-Coleska, Zaneta

AU - Miller, Rebecca

AU - Kang, Sanmao

AU - Yang, Da-Jun

AU - Wang, Shaomeng

PY - 2009/12/24

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