Caspase-1 (CASP1) (CASP1)

Caspase-1, also known as Interleukin-1 converting enzyme (ICE), is a cysteine-aspartic acid protease that plays a central role in the innate immune system (UniProt P29466). It is the primary enzyme responsible for the maturation of the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) from their inactive precursors (PubMed: 1574116). Upon activation by the inflammasome complex, such as NLRP3, Caspase-1 cleaves pro-IL-1β into its active form, which is then secreted to initiate and amplify inflammatory responses (StatPearls: NBK532865). Dysregulation of Caspase-1 and the resulting overproduction of IL-1β are implicated in a wide range of inflammatory and autoinflammatory diseases, including cryopyrin-associated periodic syndromes (CAPS), gout, and rheumatoid arthritis (Nature Reviews Drug Discovery, 2017). Therapeutic strategies targeting Caspase-1, such as the small-molecule inhibitor Belnacasan (VX-765), aim to reduce systemic inflammation by blocking the production of these potent cytokines (ClinicalTrials.gov: NCT00205465). While several inhibitors have been developed, clinical challenges include maintaining efficacy and managing the risk of immunosuppression, as Caspase-1 also mediates pyroptosis, a form of programmed cell death (Journal of Leukocyte Biology, 2020).

Other names

Interleukin-1 converting enzymeICEIL-1 beta-converting enzymeP45Caspase 1

Inhibition of the cysteine protease activity of Caspase-1, preventing the proteolytic cleavage of pro-IL-1β and pro-IL-18 into their mature, bioactive forms.