Interleukin-1β converting enzyme (ICE) : A comprehensive review on discovery and development of caspase-1 inhibitors
Copyright © 2023 Elsevier Masson SAS. All rights reserved..
Caspase-1 is a critical mediator of the inflammatory process by activating various pro-inflammatory cytokines such as pro-IL-1β, IL-18 and IL-33. Uncontrolled activation of caspase-1 leads to various cytokines-mediated diseases. Thus, inhibition of Caspase-1 is considered therapeutically beneficial to halt the progression of such diseases. Currently, rilonacept, canakinumab and anakinra are in use for caspase-1-mediated autoinflammatory diseases. However, the poor pharmacokinetic profile of these peptides limits their use as therapeutic agents. Therefore, several peptidomimetic inhibitors have been developed, but only a few compounds (VX-740, VX-765) have advanced to clinical trials; because of their toxic profile. Several small molecule inhibitors have also been progressing based on the three-dimensional structure of caspase-1. However there is no successful candidate available clinically. In this perspective, we highlight the mechanism of caspase-1 activation, its therapeutic potential as a disease target and potential therapeutic strategies targeting caspase-1 with their limitations.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:261 |
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| Enthalten in: |
European journal of medicinal chemistry - 261(2023) vom: 05. Dez., Seite 115861 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Modi, Palmi [VerfasserIn] |
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| Links: |
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| Themen: |
Autoinflammatory diseases |
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| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 03.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2023.115861 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Caspase-1 is a critical mediator of the inflammatory process by activating various pro-inflammatory cytokines such as pro-IL-1β, IL-18 and IL-33. Uncontrolled activation of caspase-1 leads to various cytokines-mediated diseases. Thus, inhibition of Caspase-1 is considered therapeutically beneficial to halt the progression of such diseases. Currently, rilonacept, canakinumab and anakinra are in use for caspase-1-mediated autoinflammatory diseases. However, the poor pharmacokinetic profile of these peptides limits their use as therapeutic agents. Therefore, several peptidomimetic inhibitors have been developed, but only a few compounds (VX-740, VX-765) have advanced to clinical trials; because of their toxic profile. Several small molecule inhibitors have also been progressing based on the three-dimensional structure of caspase-1. However there is no successful candidate available clinically. In this perspective, we highlight the mechanism of caspase-1 activation, its therapeutic potential as a disease target and potential therapeutic strategies targeting caspase-1 with their limitations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Autoinflammatory diseases | |
| 650 | 4 | |a Caspase-1 | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Peptidomimetics | |
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| 700 | 1 | |a Shah, Bhumi M |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Shivani |e verfasserin |4 aut | |
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