887588-06-9Relevant academic research and scientific papers
Selective Inhibitors of G2019S-LRRK2 Kinase Activity
Garofalo, Albert W.,Bright, Jessica,De Lombaert, Stéphane,Toda, Alyssa M. A.,Zobel, Kerry,Andreotti, Daniele,Beato, Claudia,Bernardi, Silvia,Budassi, Federica,Caberlotto, Laura,Gao, Peng,Griffante, Cristiana,Liu, Xinying,Mengatto, Luisa,Migliore, Marco,Sabbatini, Fabio Maria,Sava, Anna,Serra, Elena,Vincetti, Paolo,Zhang, Mingliang,Carlisle, Holly J.
, p. 14821 - 14839 (2020/11/30)
Pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase the risk for developing Parkinson's disease in a dominantly inherited fashion. These pathogenic variants, of which G2019S is the most common, cause abnormally high kinase activity, and compounds that inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular processes, developing inhibitors that can selectively target the pathogenic variant while sparing normal LRRK2 activity could offer potential advantages in heterozygous carriers. We conducted a high-throughput screen and identified a single selective compound that preferentially inhibited G2019S-LRRK2. Optimization of this scaffold led to a series of novel, potent, and highly selective G2019S-LRRK2 inhibitors.
FUSED TETRAZOLES AS LRRK2 INHIBITORS
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, (2019/12/04)
The present invention is directed to fused tetrazoles of formula (IA) which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.
