Pyroptosis and NETosis: Key Drivers of Inflammatory Disease
Gasdermin: An Exciting New Target in Inflammation
New Opportunities, Broad Impact
While biologic drugs on the market target the inflammatory cytokine IL-1β, these drugs do not inhibit the activity of other inflammatory cytokines and alarmins that are released by dying cells. There are no marketed therapies specifically targeting inflammatory cell death. Inflammasome-targeting drugs are in development to selectively inhibit NLRP3, a key protein in the canonical inflammasome complex. However, these molecules differ from Gasdermin D inhibitors, as they do not inhibit the activity of other NLR, pyrin or AIM2 inflammasomes, nor do they inhibit the non-canonical inflammasome or NETosis cell death pathways.
The discovery of Gasdermin D provides the missing link that connects multiple inflammatory cell death pathways. Quench Bio recognizes the tremendous therapeutic opportunity at hand and is using orthogonal approaches to discover and develop small molecule inhibitors of Gasdermin D. Unlike other therapeutic approaches, targeting Gasdermin D affords us the ability to inhibit multiple inflammatory cell death pathways simultaneously. We believe that inhibiting Gasdermin D will lead to therapeutics with the potential to reduce inflammatory cytokines, alarmins and NETs, providing benefit to patients suffering from a range of inflammatory diseases.