Table 1 Potential therapeutic agents targeting the inflammatory pathways in myelodysplastic syndromes
Target Molecule | Drug | Phase | Type of MDS | Proposed mechanism | References |
|---|---|---|---|---|---|
TLR2 | Tomaralimab (OPN-305) | I/II | Low | IgG4 monoclonal antibody against TLR2 | NCT02363491 |
TLR2 | Bortezomib | II | Low | TRAF6 inhibitor via bortezomib-mediated autophagy | NCT01891968 |
IRAK4 | Emavusertib (CA-4948) | II | High risk | IRAK4 inhibitor | NCT04278768 |
TGF-Beta | Luspatercept | III | Low | Binds to endogenous TGF-β superfamily ligands, thereby diminishing Smad2/3 signaling. | NCT02621070 (MEDALIST trial) |
TGF-Beta | Galunisertib | II | Low | Inhibitor of the TGF-β receptor type 1 kinase (ALK5) | NCT02008318 |
Inflammasome | MCC950 | Preclinical | Â | Blocks the NACTH ATPase domain of NLRP3 | Ashley A et al. [65] |
Inflammasome | 3,4 methylenedioxy-β-nitrostyrene (MNS) | Preclinical |  | Inhibits NLRP3 ATPase activity by cysteine modification | Chakraborty et al. [66] |
Inflammasome | CY-09 | Preclinical | Â | Inhibits NLRP3 ATPase activity to block NLRP3 activation | Jiang Hua et al. [67] |
Inflammasome | Ibrutinib | I | High | BTK inhibitor; directly binds ASC and NLRP3; inh ASC speck formation | NCT03359460 |
P38 MAPK | Pexmetinib (ARRY614) | I | Low or intermediate | Enhancing Megakaryopoiesis | NCT01496495 |
P38 MAPK | Talmapimod (SCIO-469) | II | Low | Enhancement of Hematopoiesis and reduction of apoptosis | NCT00113893 |
IL-8 receptor/CXCR2 | SB-332,235 | Preclinical | Â | Reduction of growth and colony forming in MDS BM cells | Schinke C et al. [93] |
IL-8 | BMS-986,253 | I/II | Â | Anti-il-8 monoclonal antibody | NCT05148234 |
Caspase | CWP232291 | 1 | High risk | Inhibitor of Wnt signaling that causes degradation of β-catenin via apoptosis | NCT01398462 |