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Title
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Inhibitors targeting RIPK1/RIPK3 : old and new drugs
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Author
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Abstract
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| The scaffolding function of receptor-interacting protein kinase 1 (RIPK1) regulates prosurvival signaling and inflammatory gene expression, while its kinase activity mediates both apoptosis and necroptosis; the latter involving RIPK3 kinase activity. The mutual transition between the scaffold and kinase functions of RIPK1 is regulated by (de)ubiquitylation and (de)phosphorylation. RIPK1-mediated cell death leads to disruption of epithelial barriers and/or release of damage-associated molecular patterns (DAMPs), cytokines, and chemokines, propagating inflammatory and degenerative diseases. Many drug development programs have pursued targeting RIPK1, and to a lesser extent RIPK3 kinase activity. In this review, we classify existing and novel small-molecule drugs based on their pharmacodynamic (PD) type I, II, and III binding mode. Finally, we discuss their applicability and therapeutic potential in inflammatory and degenerative experimental disease models. |
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Language
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English
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Source (journal)
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Trends in pharmacological sciences. - Amsterdam
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Publication
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London
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Elsevier science london
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2020
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ISSN
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0165-6147
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DOI
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10.1016/J.TIPS.2020.01.002
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Volume/pages
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41
:3
(2020)
, p. 209-224
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ISI
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000514828300008
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Pubmed ID
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32035657
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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