Patented inhibitors of p53-Mdm2 interaction (2006 - 2008).
BACKGROUND
Induction of apoptosis by reactivation of p53 in cancer cells is an emerging therapeutic concept for the treatment of cancer. The discovery and design of novel small molecules that block the p53-Mdm2 protein interaction, thereby activating p53, has provided interesting drug candidates that have currently entered clinical trials or are at the preclinical development stage.


METHODS
A selection of the interesting patents focusing on small molecule inhibitors of the p53-Mdm2 interaction, recorded from 2006 until 2009, is presented together with a review of the related structural chemistry space.


RESULTS
Readers will rapidly gain an overview of the majority of patented scaffolds of small molecule inhibitors of the p53-Mdm2 protein-protein interaction and learn about current limitations and properties of these compounds.


CONCLUSIONS
The discovery p53-Mdm2 protein-protein interaction inhibitors have delivered new potential options for a targeted cancer therapy with drug-like, non-toxic small molecules. If successful, this approach could gain considerably more attention in the pharmaceutical industry by targeting a variety of validated intracellular protein-protein interactions.
Weber
Lutz
L
NexusPharma, Inc., #253-13 Summit Square Center, Langhorne, PA 19047-1098, USA. lutz.weber@nexuspharm.com
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010330:Patents as Topic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2