GSK2578215A : a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. / Reith, Alastair D.; Bamborough, Paul; Jandu, Karamjit; Andreotti, Daniele; Mensah, Lucy; Dossang, Pamela; Choi, Hwan Geun; Deng, Xianming; Zhang, Jinwei; Alessi, Dario R.; Gray, Nathanael S.
In: Bioorganic & Medicinal Chemistry Letters, Vol. 22, No. 17, 2012, p. 5625-5629.Research output: Contribution to journal › Article
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TY - JOUR
T1 - GSK2578215A
T2 - a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor
A1 - Reith,Alastair D.
A1 - Bamborough,Paul
A1 - Jandu,Karamjit
A1 - Andreotti,Daniele
A1 - Mensah,Lucy
A1 - Dossang,Pamela
A1 - Choi,Hwan Geun
A1 - Deng,Xianming
A1 - Zhang,Jinwei
A1 - Alessi,Dario R.
A1 - Gray,Nathanael S.
AU - Reith,Alastair D.
AU - Bamborough,Paul
AU - Jandu,Karamjit
AU - Andreotti,Daniele
AU - Mensah,Lucy
AU - Dossang,Pamela
AU - Choi,Hwan Geun
AU - Deng,Xianming
AU - Zhang,Jinwei
AU - Alessi,Dario R.
AU - Gray,Nathanael S.
PY - 2012
Y1 - 2012
N2 - Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for some forms of Parkinson's disease. Here we report the discovery and characterization of 2-arylmethyloxy-5-subtitutent-N-arylbenzamides with potent LRRK2 activities exemplified by GSK2578215A which exhibits biochemical IC s of around 10 nM against both wild-type LRRK2 and the G2019S mutant. GSK2578215A exhibits exceptionally high selectivity for LRRK2 across the kinome, substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.3-1.0 µM in cells and in mouse spleen and kidney, but not in brain, following intraperitoneal injection of 100 mg/kg. © 2012 Elsevier Ltd. All rights reserved.
AB - Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for some forms of Parkinson's disease. Here we report the discovery and characterization of 2-arylmethyloxy-5-subtitutent-N-arylbenzamides with potent LRRK2 activities exemplified by GSK2578215A which exhibits biochemical IC s of around 10 nM against both wild-type LRRK2 and the G2019S mutant. GSK2578215A exhibits exceptionally high selectivity for LRRK2 across the kinome, substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.3-1.0 µM in cells and in mouse spleen and kidney, but not in brain, following intraperitoneal injection of 100 mg/kg. © 2012 Elsevier Ltd. All rights reserved.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84864401977&md5=f9bfcb42ed8b7f832def295aeeef1e6d
U2 - 10.1016/j.bmcl.2012.06.104
DO - 10.1016/j.bmcl.2012.06.104
M1 - Article
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
SN - 0960-894X
IS - 17
VL - 22
SP - 5625
EP - 5629
ER -