title: Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011-present).
abstract: BACKGROUND
  One of the hallmarks of cancer cells is the inactivation of the p53 pathway either due to mutations in the p53 gene or over-expression of negative regulators, Mdm2 and/or MdmX. Pharmacological disruption of the Mdm2/X-p53 interaction to restore p53 activity is an attractive concept, aiming at a targeted and non-toxic cancer treatment.
  
  
  METHODS
  The introduction covers the biological role of p53 pathway and its regulation by Mdm2 and MdmX in normal and cancer cells and the current repertoire and development status of inhibitors of the Mdm2/X-p53 interaction for the treatment of cancer. The main part of the article covers patents and patent applications describing small molecule inhibitors of the Mdm2/X-p53 interaction published from 2011 until 2012.
  
  
  CONCLUSIONS
  The area of small molecule Mdm2/X-p53 interaction inhibitor development is progressing fast. Several Phase I clinical studies and preclinical programs are now in progress, however, the clinical proof concept has yet to be demonstrated. Multiple available compounds inhibit Mdm2-p53 interaction with nanomolar affinities, but MdmX is still missing such potent binders. Since research points to a complementary mode of Mdm2 and MdmX action, the future compound classes will possibly want to include dual actions versus Mdm2 and MdmX.
authors: Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Kraków, Poland.
authors: Krzysztof
authors: K
authors: Zak
authors: Aleksandra
authors: A
authors: Pecak
authors: Barbara
authors: B
authors: Rys
authors: Benedykt
authors: B
authors: Wladyka
authors: Alexander
authors: A
authors: Dömling
authors: Lutz
authors: L
authors: Weber
authors: Tad A
authors: TA
authors: Holak
authors: Grzegorz
authors: G
authors: Dubin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004335:Drug and Narcotic Control; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010330:Patents as Topic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051736:Proto-Oncogene Proteins c-mdm2