1. Academic Validation
  2. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

  • Cell Chem Biol. 2017 Mar 16;24(3):281-292. doi: 10.1016/j.chembiol.2017.02.003.
Christina E Smith 1 Subada Soti 1 Torey A Jones 1 Akihisa Nakagawa 2 Ding Xue 2 Hang Yin 3
Affiliations

Affiliations

  • 1 Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
  • 2 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
  • 3 Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: hubert.yin@colorado.edu.
Abstract

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 in 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.

Keywords

NSAIDs; anti-inflammation; caspase; pharmacology.

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