Summary of inflammation-targeted agents in clinical or preclinical development for myeloid malignancies
| Target . | Molecule . | Mechanism . | Combination . | Disease . | Phase . | Registration or PMID . | Status . |
|---|---|---|---|---|---|---|---|
| Cell-intrinsic targets | |||||||
| TLR2 | OPN-305 | Anti-TLR2 MAB | HMA | MDS | 1/2 | NCT02363491 | Completed |
| TLR4 | Bortezomib | Proteasome inhibitor | NA | MDS | 2 | NCT01891968 | Completed |
| TLR9 | GNKG168 | Small molecule agonist | None | AML/ALL | 1 | NCT01743807 | Terminated |
| IRAK1 | IRAK-Inh | Small molecule inhibitor | NA | MDS | Preclinical | 23845443 | NA |
| IRAK4 | CA-4948 | Inhibits long isoform | HMA or Venetoclax | MDS/AML | 1/2a | NCT04278768 | Recruiting |
| TRAF6 | NSC697923 | UBE2N cofactor inhibitor | NA | MDS/AML | Preclinical | Blood. 2016;128(22):579 | NA |
| NLRP3 | MCC-950 | NACTH ATPase domain inhibitor | NA | MDS | Preclinical | 31086327 | NA |
| MNS | Blocks cysteine modification | NA | MDS | Preclinical | 24265316 | NA | |
| CY-09 | Blocks NLRP3 activation | NA | MDS | Preclinical | 33765556 | NA | |
| Ibrutinib | BTK inhibitor | HMA | MDS | 1b | NCT02553941 | Active | |
| Caspase-1 | VX-765 | Peptidomimetic drug | NA | Epilepsy | 2 | NCT01048255 | Completed |
| Psoriasis | NCT00205465 | Completed | |||||
| cGAS-STING | Pending | NA | NA | MDS/AML | Preclinical | 33329537 | NA |
| Cell-extrinsic targets | |||||||
| TGF-β | Luspatercept | Ligand trap | None | MDS | 3 | 31914241 | Published |
| IL-1β | Canakinumab | MAB | HMA | MDS | 2 | NCT04239157 | Recruiting |
| IL-6 | Siltuximab | MAB | NA | MDS/AML | Preclinical | 32269167 | NA |
| Tocilizumab | |||||||
| HMGB1 | CX-01 | Small molecule inhibitor | HMA | MDS/AML | 1 | NCT02995655 | Completed |
| S100A8/9 | Pending | NA | NA | MDS/AML | Preclinical | 27666011 | NA |
| Target . | Molecule . | Mechanism . | Combination . | Disease . | Phase . | Registration or PMID . | Status . |
|---|---|---|---|---|---|---|---|
| Cell-intrinsic targets | |||||||
| TLR2 | OPN-305 | Anti-TLR2 MAB | HMA | MDS | 1/2 | NCT02363491 | Completed |
| TLR4 | Bortezomib | Proteasome inhibitor | NA | MDS | 2 | NCT01891968 | Completed |
| TLR9 | GNKG168 | Small molecule agonist | None | AML/ALL | 1 | NCT01743807 | Terminated |
| IRAK1 | IRAK-Inh | Small molecule inhibitor | NA | MDS | Preclinical | 23845443 | NA |
| IRAK4 | CA-4948 | Inhibits long isoform | HMA or Venetoclax | MDS/AML | 1/2a | NCT04278768 | Recruiting |
| TRAF6 | NSC697923 | UBE2N cofactor inhibitor | NA | MDS/AML | Preclinical | Blood. 2016;128(22):579 | NA |
| NLRP3 | MCC-950 | NACTH ATPase domain inhibitor | NA | MDS | Preclinical | 31086327 | NA |
| MNS | Blocks cysteine modification | NA | MDS | Preclinical | 24265316 | NA | |
| CY-09 | Blocks NLRP3 activation | NA | MDS | Preclinical | 33765556 | NA | |
| Ibrutinib | BTK inhibitor | HMA | MDS | 1b | NCT02553941 | Active | |
| Caspase-1 | VX-765 | Peptidomimetic drug | NA | Epilepsy | 2 | NCT01048255 | Completed |
| Psoriasis | NCT00205465 | Completed | |||||
| cGAS-STING | Pending | NA | NA | MDS/AML | Preclinical | 33329537 | NA |
| Cell-extrinsic targets | |||||||
| TGF-β | Luspatercept | Ligand trap | None | MDS | 3 | 31914241 | Published |
| IL-1β | Canakinumab | MAB | HMA | MDS | 2 | NCT04239157 | Recruiting |
| IL-6 | Siltuximab | MAB | NA | MDS/AML | Preclinical | 32269167 | NA |
| Tocilizumab | |||||||
| HMGB1 | CX-01 | Small molecule inhibitor | HMA | MDS/AML | 1 | NCT02995655 | Completed |
| S100A8/9 | Pending | NA | NA | MDS/AML | Preclinical | 27666011 | NA |
BTK, Bruton’s tyrosine kinase; cGAS-STING, cyclic GMP-AMP synthase stimulator of interferon genes; HMA, hypomethylating agent; MAB, monoclonal antibody; NA, not available; TLR, toll-like receptor.
Current from 30 November 2021.