title: Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape.
abstract: BACKGROUND
  Akt plays a pivotal role in cell survival and proliferation through a number of downstream effectors; unregulated activation of the PI3K/PTEN/Akt pathway is a prominent feature of many human cancers. Akt is considered an attractive target for cancer therapy by the inhibition of Akt alone or in combination with standard cancer chemotherapeutics. Both preclinical animal studies and clinical trials in humans have validated Akt as an important target of cancer drug discovery.
  
  
  METHODS
  A historical perspective of Akt inhibitors, including PI analogs, ATP-competitive and allosteric Akt inhibitors, along with other inhibitory mechanisms are reviewed in this paper with a focus on issued patents, patent applications and a summary of clinical trial updates since the last review in 2007.
  
  
  CONCLUSIONS
  A vast diversity of inhibitors of Akt, both small molecule and biologic, have been developed in the past 5 years, with over a dozen in various phases of clinical development, and several displaying efficacy in humans. While it is not yet clear which mechanism of Akt inhibition will be optimal in humans, or which Akt isoforms to inhibit, or whether a small molecule or biologic agent will be best, data to all of these points will be available in the near future.
authors.affiliation: Vanderbilt University, Vanderbilt Medical Center, Vanderbilt Program in Drug Discovery, Department of Pharmacology , Department of Chemistry , Nashville, TN 37232 , USA.
authors.forename: Margrith E
authors.initials: ME
authors.lastname: Mattmann
authors.forename: Sydney L
authors.initials: SL
authors.lastname: Stoops
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D010330:Patents as Topic; D054852:Small Molecule Libraries
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D054852:Small Molecule Libraries; D000255:Adenosine Triphosphate; D051058:Oncogene Protein v-akt