Abstract
Increasing knowledge of the relationship between p53 and MDM2 has led to development of potential small molecule inhibitors useful for clinical studies. Herein, we discuss the patented (2006-2010) inhibitors of p53-MDM2 interaction. The anticancer agents discussed in this review belong to several different chemical classes including benzodiazepinediones, cis-imidazolines, oxindoles, spirooxindoles, and numerous miscellaneous groups. This review also provides comprehensive information on inhibitors of p53-MDM2 interaction that are currently being tested in clinical trials. It is important to note that many of the disclosed inhibitors need further validation to be considered as bona fide inhibitors of p53-MDM2 interaction and some will not be further considered for future studies. On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients. AT-219, a spiroindolinone in late stage preclinical studies is a likely candidate to proceed into clinical trials. It remains to be seen how these inhibitors will perform in future clinical studies as single agents and in combination with the currently approved chemotherapeutic agents.
Keywords: p53, MDM2, protein-protein interaction, nutlin, benzodiazepinediones, cis-imidazolines, oxindoles, spiro-oxindoles, small molecule anticancer agents, MDM2 antagonists, p53 wild type, spiroindolinone, JNJ- 26854165, RG7112, AT-219
Current Pharmaceutical Design
Title: Small-Molecule Inhibitors of p53-MDM2 Interaction: the 2006-2010 Update
Volume: 17 Issue: 6
Author(s): Melissa Millard, Divya Pathania, Fedora Grande, Shili Xu and Nouri Neamati
Affiliation:
Keywords: p53, MDM2, protein-protein interaction, nutlin, benzodiazepinediones, cis-imidazolines, oxindoles, spiro-oxindoles, small molecule anticancer agents, MDM2 antagonists, p53 wild type, spiroindolinone, JNJ- 26854165, RG7112, AT-219
Abstract: Increasing knowledge of the relationship between p53 and MDM2 has led to development of potential small molecule inhibitors useful for clinical studies. Herein, we discuss the patented (2006-2010) inhibitors of p53-MDM2 interaction. The anticancer agents discussed in this review belong to several different chemical classes including benzodiazepinediones, cis-imidazolines, oxindoles, spirooxindoles, and numerous miscellaneous groups. This review also provides comprehensive information on inhibitors of p53-MDM2 interaction that are currently being tested in clinical trials. It is important to note that many of the disclosed inhibitors need further validation to be considered as bona fide inhibitors of p53-MDM2 interaction and some will not be further considered for future studies. On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients. AT-219, a spiroindolinone in late stage preclinical studies is a likely candidate to proceed into clinical trials. It remains to be seen how these inhibitors will perform in future clinical studies as single agents and in combination with the currently approved chemotherapeutic agents.
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Cite this article as:
Millard Melissa, Pathania Divya, Grande Fedora, Xu Shili and Neamati Nouri, Small-Molecule Inhibitors of p53-MDM2 Interaction: the 2006-2010 Update, Current Pharmaceutical Design 2011; 17 (6) . https://dx.doi.org/10.2174/138161211795222649
DOI https://dx.doi.org/10.2174/138161211795222649 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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