Abstract
This review provides an overview of the biochemistry and activation of inflammatory caspases, and focuses on their therapeutic potential as disease targets in pathologies such as sepsis, Crohns disease, rheumatoid arthritis, traumatic brain injury and amyotrophic lateral sclerosis (ALS). We summarize the proof-of-principal evidence obtained by studies in several corresponding experimental disease models confirming the validity of strategies targeting inflammatory caspases. We discuss the use of inflammatory caspase inhibitors, such as VX-740 (Pralnacasan) and VX-765, in clinical studies for rheumatoid arthritis and osteoarthritis. Finally, we point out recent approaches identifying novel peptidomimetic or non-peptide caspase inhibitors with suitable clinical profiles.
Keywords: Peptide inhibitor, caspases, apoptosis, neurodegeneration, inflammation, inflammasome, utoimmune disease, pralnacasan, animal model
Current Pharmaceutical Design
Title: Inflammatory Caspases: Targets for Novel Therapies
Volume: 13 Issue: 4
Author(s): Sigrid Cornelis, Kristof Kersse, Nele Festjens, Mohamed Lamkanfi and Peter Vandenabeele
Affiliation:
Keywords: Peptide inhibitor, caspases, apoptosis, neurodegeneration, inflammation, inflammasome, utoimmune disease, pralnacasan, animal model
Abstract: This review provides an overview of the biochemistry and activation of inflammatory caspases, and focuses on their therapeutic potential as disease targets in pathologies such as sepsis, Crohns disease, rheumatoid arthritis, traumatic brain injury and amyotrophic lateral sclerosis (ALS). We summarize the proof-of-principal evidence obtained by studies in several corresponding experimental disease models confirming the validity of strategies targeting inflammatory caspases. We discuss the use of inflammatory caspase inhibitors, such as VX-740 (Pralnacasan) and VX-765, in clinical studies for rheumatoid arthritis and osteoarthritis. Finally, we point out recent approaches identifying novel peptidomimetic or non-peptide caspase inhibitors with suitable clinical profiles.
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Cite this article as:
Cornelis Sigrid, Kersse Kristof, Festjens Nele, Lamkanfi Mohamed and Vandenabeele Peter, Inflammatory Caspases: Targets for Novel Therapies, Current Pharmaceutical Design 2007; 13 (4) . https://dx.doi.org/10.2174/138161207780163006
DOI https://dx.doi.org/10.2174/138161207780163006 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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