title: Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 - 2013).
abstract: BACKGROUND
  Leucine-rich repeat kinase 2 (LRRK2) is a large (2527 residues) complex multi-domain protein that has GTPase and kinase domains. Autosomal dominant missense mutations in LRRK2 have been found in individuals with Parkinson's disease (PD) and are considered responsible for 1% of all cases of PD. Among the mutations confirmed to contribute to PD pathogenicity, G2019S is the most common cause of PD and it increases the kinase activity of LRRK2 by around threefold. LRRK2 has received considerable attention as a therapeutic target for PD, and LRRK2 inhibitors may help prevent and/or treat the disease.
  
  
  METHODS
  LRRK2 inhibitors are being investigated by various industrial and academic institutions. The present review covers patents literature on small-molecule LRRK2 inhibitors patented between 2011 and 2013.
  
  
  CONCLUSIONS
  Currently, wild-type and mutant LRRK2 are being examined as therapeutic targets for PD. In testimony to the significance of these novel targets, over 20 patent applications related to LRRK2 have been filed in the last 3 years. Several distinct chemotypes have been reported to be LRRK2 inhibitors with very good potency. These compounds are being used to elucidate the physiological and pathophysiological functions of LRRK2, and some may even emerge as therapeutics for PD.
authors.affiliation: Department of Medicinal Chemistry, Jubilant Biosys , 96 Industrial Suburb, IInd stage, Bangalore-560022 , India.
authors.forename: Raghava R
authors.initials: RR
authors.lastname: Kethiri
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Bakthavatchalam
mesh_terms: D000818:Animals; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics*; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: G2019S mutation; Parkinson's disease; blood–brain barrier; kinase inhibitors; l-DOPA; leucine-rich repeat kinase 2; leucine-rich repeat kinase 2 inhibitors; neurodegenerative disease; wild-type leucine-rich repeat kinase 2