Recent advances in the therapeutic perspectives of Nutlin-3.

Abstract

Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53(wild-type) status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.

• Authors: Paola Secchiero, Raffaella Bosco, Claudio Celeghini, Giorgio Zauli
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 17 Issue 6 Pg. 569-77 ( 2011) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 21391907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Imidazoles
• Piperazines
• Tumor Suppressor Protein p53
• nutlin 3
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Drug Synergism
• Genes, p53 (drug effects, physiology)
• Humans
• Imidazoles (pharmacology)
• Neoplasms (drug therapy, genetics, metabolism)
• Piperazines (pharmacology)
• Proto-Oncogene Proteins c-mdm2 (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)