Selective Inhibitors of G2019S-LRRK2 Kinase Activity
| العنوان: | Selective Inhibitors of G2019S-LRRK2 Kinase Activity |
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| المؤلفون: | Peng Gao, Paolo Vincetti, Fabio Maria Sabbatini, Holly J. Carlisle, Luisa Mengatto, Stéphane De Lombaert, Anna Sava, Kerry Zobel, Xinying Liu, Claudia Beato, Jessica M. Bright, Alyssa M. A. Toda, Elena Serra, Federica Budassi, Marco Migliore, Laura Caberlotto, Cristiana Griffante, Silvia Bernardi, Mingliang Zhang, Albert W. Garofalo, Daniele Andreotti |
| المصدر: | Journal of Medicinal Chemistry. 63:14821-14839 |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Indazoles, Tetrazoles, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, 01 natural sciences, Small Molecule Libraries, Mice, Structure-Activity Relationship, 03 medical and health sciences, Drug Discovery, Animals, Humans, Kinase activity, Protein Kinase Inhibitors, Gene, 030304 developmental biology, 0303 health sciences, Molecular Structure, Chemistry, Kinase, Highly selective, LRRK2, High-Throughput Screening Assays, nervous system diseases, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, HEK293 Cells, Pyrimidines, Mutation, Cancer research, Molecular Medicine |
| الوصف: | 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. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::093ee26c9e2bb68692138fc7ec600a40 https://doi.org/10.1021/acs.jmedchem.0c01243 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....093ee26c9e2bb68692138fc7ec600a40 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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