Table 3.
Current pharmacological strategies for modulation of pyroptosis
| Target | Drug | Phase | References/ Clinical Trials |
|---|---|---|---|
| Inhibitors of Pyroptosis | |||
| NLRP3 | MCC950 | Failed Phase 2 trial in rheumatoid arthritis patients due to hepatotoxicity | [164] |
| Inzomelid | Completed Phase 1 | NCT04015076 | |
| IZD334 | Completed Phase 1 | NCT04086602 | |
| Tranilast | Approved outside the US for asthma, keloids, and conjunctivitis; Phase 2 trial ongoing in CAPS patients | NCT03923140 | |
| DFV890 (IFM-2427) | Phase 2 trials for knee osteoarthritis, FACS, and COVID-19 | NCT04868968; NCT04886258; NCT04382053 | |
| Dapansutrile | Phase 2 trial completed for gout and in progress for CRS | [168]; NCT04540120 | |
| RRx-001 | Phase 3 for oncology applications | [167] | |
| CY-09 | Pre-clinical | [169] | |
| Oridonin | Pre-clinical | [166] | |
| INF39 | Pre-clinical | [170] | |
| Caspase-1 | Pralnacasan (VX-740) | Failed Phase 2 trial in rheumatoid arthritis patients due to hepatotoxicity | [175] |
| Belnacasan (VX-765) | Failed to meet primary endpoints in Phase 2 trial in epilepsy patients | [175,178] | |
| GSDMD | Necrosulfonamide | Pre-clinical | [44] |
| Disulfiram | Approved for alcohol dependence; Phase 1–3 for oncology applications | [45,171] | |
| Dimethyl fumarate | Approved in the US for multiple sclerosis; Approved in the EU for plaque psoriasis | [172] | |
| Unknown | Punicalagin | Pre-clinical | [200] |
| LDC7559 | Pre-clinical | [138] | |
| Activators of Pyroptosis | |||
| NLRP1/ CARD8 | Val-boroPro (talabostat, BXCL701) | Phase 1–3 for oncology applications | NCT03910660; NCT03910660; NCT04171219 |
| NLRP3 | BMS-986299 | Phase 1 | NCT03444753 |
| GSDMA | Nanoparticle-conjugated delivery of GSDMA3 | Pre-clinical | [199] |
| GSDMD | AAV delivery of GSDMDNT | Pre-clinical | [198] |
AAV = adeno-associated virus; EU = European Union