Table 3.
Drugs in development over the past decade targeting the IL-1 pathway
| Drug | Target | Mechanism | Clinical Trial |
|---|---|---|---|
| CE-224535 | P2X7 | Selective P2X(7) receptor antagonist | NCT00628095 |
| AZD9056 | P2X7 | Selective P2X(7) receptor antagonist | NCT00520572 |
| BMS-986299 | NLRP3 | Agonist | NCT03444753 |
| Dapansutrile | NLRP3 | Small molecular inhibitor | NCT03595371 |
| IZD334 | NLRP3 | Small molecule inhibitor | NCT04086602 |
| ZYIL1 | NLRP3 | Small molecule inhibitor | NCT04731324 |
| IZD174 | NLRP3 | Small molecule inhibitor, CNS penetrant | NCT04338997 |
| AC-201 | NLRP3 | Small molecule inhibitor | NCT02287818 |
| VX-765 | Caspase 1 | Small molecule inhibitor | NCT00205465 |
| Emricasan | Caspase 1 | Pan caspase inhibitor | NCT04803227 |
| Disulfiram | GSDMD | Gasdermin D inhibitor | NCT04485130 |
| Bermekimab | IL-1α | Anti-IL-1α monoclonal antibody | NCT03512275 |
| Gevokizumab | IL-1β | Anti-IL-1β monoclonal antibody | NCT01211977 |
| LY2189102 | IL-1β | Anti-IL-1β humanized monoclonal immunoglobulin G4 | NCT00380744 |
| CYT013-IL1bQb | IL-1β | Vaccine to IL-1β | NCT00924105 |
| Lutikizumab | IL-1α/IL-1β | Dual affinity monoclonal antibody to IL-1α/IL-1β | NCT01668511 |
| MAS825 | IL-1β/IL-18 | Bispecific IL-1β and IL-18 monoclonal antibody | NCT04641442 |
| sc-rAAV2.5IL-1Ra | IL-1R1 | Self-complementing, recombinant AAV carrying IL-1RA cDNA | NCT02790723 |
| EBI-005 | IL-1R1 | IL-1β and IL-1 receptor antagonist fusion protein | NCT04121442 |
| HL2351 | IL-1R1 | Human IL-1Ra-hyFc | NCT02853084 |
| MEDI8968 | IL-1R1 | Anti-IL-1R1 human monoclonal antibody | NCT01838499 |
| AMG108 | IL-1R1 | Anti-IL-1R1 monoclonal antibody | NCT00110942 |
| EBI-005 | IL-1R1 | Chimeric IL-1RA- IL-1β | NCT02082899 |
| KT-474 | IRAK4 | Oral heterobifunctional small molecule IRAK4 degrader | NCT04772885 |
| ATI-450 | MK2 | Oral small molecule MAPKAPK2 (MK2) inhibitor | NCT04524858 |
Identified based on search terms IL-1, inflammasome, NLRP3, at clinicaltrials.gov and Dinarello et al.92.