Targeting protein kinases in central nervous system disorders
Identifieur interne : 000948 ( Main/Exploration ); précédent : 000947; suivant : 000949Targeting protein kinases in central nervous system disorders
Auteurs : Laura K. Chico [États-Unis] ; Linda J. Van Eldik [États-Unis] ; D. Martin Watterson [États-Unis]Source :
- Nature Reviews Drug Discovery [ 1474-1776 ] ; 2009-11.
Abstract
Protein kinases are a growing drug target class in disorders in peripheral tissues, but the development of kinase-targeted therapies for central nervous system (CNS) diseases remains a challenge, largely owing to issues associated specifically with CNS drug discovery. However, several candidate therapeutics that target CNS protein kinases are now in various stages of preclinical and clinical development. We review candidate compounds and discuss selected CNS protein kinases that are emerging as important therapeutic targets. In addition, we analyse trends in small-molecule properties that correlate with key challenges in CNS drug discovery, such as bloodbrain barrier penetrance and cytochrome P450-mediated metabolism, and discuss the potential of future approaches that will integrate molecular-fragment expansion with pharmacoinformatics to address these challenges.
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DOI: 10.1038/nrd2999
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Martin Watterson</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:F296042F8A9FD34771E5A56C0AEF7E86FC656BC0</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1038/nrd2999</idno><idno type="url">https://api.istex.fr/document/F296042F8A9FD34771E5A56C0AEF7E86FC656BC0/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001340</idno><idno type="wicri:Area/Main/Curation">001132</idno><idno type="wicri:Area/Main/Exploration">000948</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Targeting protein kinases in central nervous system disorders</title><author><name sortKey="Chico, Laura K" sort="Chico, Laura K" uniqKey="Chico L" first="Laura K." last="Chico">Laura K. Chico</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Center for Molecular Innovation and Drug Discovery, Northwestern University, Chicago, Illinois 60611</wicri:regionArea><wicri:noRegion>Illinois 60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>LKC Pharma Services, Inc., LaGrange, Illinois 60525</wicri:regionArea><wicri:noRegion>Illinois 60525</wicri:noRegion></affiliation></author><author><name sortKey="Van Eldik, Linda J" sort="Van Eldik, Linda J" uniqKey="Van Eldik L" first="Linda J." last="Van Eldik">Linda J. Van Eldik</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Center for Molecular Innovation and Drug Discovery, Northwestern University, Chicago, Illinois 60611</wicri:regionArea><wicri:noRegion>Illinois 60611</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Cell and Molecular Biology Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611</wicri:regionArea><wicri:noRegion>Illinois 60611</wicri:noRegion></affiliation></author><author><name sortKey="Watterson, D Martin" sort="Watterson, D Martin" uniqKey="Watterson D" first="D. Martin" last="Watterson">D. 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However, several candidate therapeutics that target CNS protein kinases are now in various stages of preclinical and clinical development. We review candidate compounds and discuss selected CNS protein kinases that are emerging as important therapeutic targets. In addition, we analyse trends in small-molecule properties that correlate with key challenges in CNS drug discovery, such as bloodbrain barrier penetrance and cytochrome P450-mediated metabolism, and discuss the potential of future approaches that will integrate molecular-fragment expansion with pharmacoinformatics to address these challenges.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Chico, Laura K" sort="Chico, Laura K" uniqKey="Chico L" first="Laura K." last="Chico">Laura K. Chico</name></noRegion><name sortKey="Chico, Laura K" sort="Chico, Laura K" uniqKey="Chico L" first="Laura K." last="Chico">Laura K. 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