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NSAIDs are Caspase Inhibitors
Cell chemical biology, 2017-02, Vol.24 (3), p.281-292
2017

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Autor(en) / Beteiligte
Titel
NSAIDs are Caspase Inhibitors
Ist Teil von
  • Cell chemical biology, 2017-02, Vol.24 (3), p.281-292
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID-family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo . We characterize caspase activity both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX-independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design. Smith et al. report the identification and characterization of caspases as general NSAID pharmacological targets. Inhibition occurs at physiologically relevant concentrations both in vitro and in vivo , and expands the NSAID anti-inflammatory mechanism.
Sprache
Englisch
Identifikatoren
eISSN: 2451-9456
DOI: 10.1016/j.chembiol.2017.02.003
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5357154
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