{Reference Type}: Journal Article
{Title}: Interleukin-1β converting enzyme (ICE): A comprehensive review on discovery and development of caspase-1 inhibitors.
{Author}: Modi P;Shah BM;Patel S;
{Journal}: Eur J Med Chem
{Volume}: 261
{Issue}: 0
{Year}: 2023 Dec 5
{Factor}: 7.088
{DOI}: 10.1016/j.ejmech.2023.115861
{Abstract}: 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.