title: Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 - 2011).
abstract: BACKGROUND
  Leucine-rich repeat kinase 2 (LRRK2) has received considerable attention since the discovery of LRRK2 mutations in families with dominantly inherited Parkinson's disease (PD) in 2004. The missense mutation G2019S is the most common LRRK2 mutation and has been identified in both familial and sporadic PD cases. The G2019S mutation enhances kinase activity suggesting that LRRK2 could be an attractive therapeutic target for PD and small-molecule ATP-competitive LRRK2 kinase inhibitors are one way to investigate this possibility.
  
  
  METHODS
  Currently, LRRK2 kinase inhibitors are being actively pursued by industry and academia. Herein, patents detailing the discovery of LRRK2 kinase inhibitors from 2006 through 2011 and the corresponding publications from 2006 through July of 2012 are summarized.
  
  
  CONCLUSIONS
  Wild-type and mutant forms of LRRK2 are currently being actively pursued as therapeutic targets for the potential treatment of PD. The increasing number of patent applications being filed for inhibitors of LRRK2 is a testament to this activity. Numerous distinct chemo-types have been reported as LRRK2 inhibitors with some demonstrating exceptional potency and selectivity for LRRK2 relative to other kinases. These compounds are being used as pharmacological 'tools' to elucidate the physiological and pathophysiological function of LRRK2 and it appears likely that some will be investigated for their potential therapeutic effects for the treatment of PD.
authors.affiliation: Xiamen University, School of Life Sciences, State Key Laboratory of Cellular Stress Biology, Fujian 361005, China. xmdeng@xmu.edu.cn
authors.forename: Xianming
authors.initials: X
authors.lastname: Deng
authors.forename: Hwan Geun
authors.initials: HG
authors.lastname: Choi
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Buhrlage
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015394:Molecular Structure; D009154:Mutation; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D010330:Patents as Topic; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000978:Antiparkinson Agents; D047428:Protein Kinase Inhibitors; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases