title: BACE2 as a new diabetes target: a patent review (2010 - 2012).
abstract: BACKGROUND
  When two novel aspartyl proteases were published in 1999 and 2000, beta-site APP-cleaving enzyme 1 (BACE1) was confirmed as the long sought after beta-secretase and Alzheimer's disease drug target. However, the role of its paralogue, BACE2, proved elusive until a 2011 publication implicated it as a Collectrin (TMEM27) secretase controlling pancreatic beta-cell proliferation and a new therapeutic intervention for diabetes.
  
  
  METHODS
  This review, using SureChemOpen, encompasses early validation compounds and small-molecule BACE2 inhibitors for diabetes. Since 2010, one assay patent and several chemical series have been published by Roche but these were followed by filings from Novartis and Schering in 2012. The patents from these three companies include BACE2-only filings but also some specifying both BACE1 and BACE2 inhibitors.
  
  
  CONCLUSIONS
  Roche's early collaborative target validation has given them a lead in BACE2 medicinal chemistry. However, the extensive data output for BACE1 in patents and papers over the last decade, plus liganded crystal structures for both proteases, should expedite the design of BACE2 inhibitors by other organisations. This may also shorten the development time for clinical candidates that, unlike those now entering Phase I trials for BACE1, would not need to be brain-penetrant.
authors.affiliation: TW2Informatics Ltd, Göteborg, Sweden. cdsouthan@hotmail.com
authors.forename: Christopher
authors.initials: C
authors.lastname: Southan
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010330:Patents as Topic
chemical_list: D007004:Hypoglycemic Agents; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human