subasumstat

Subasumstat (TAK-981) is a first-in-class, small molecule inhibitor of the SUMO-activating enzyme (SAE), also known as the SUMO E1 enzyme. Developed by Takeda, it works by forming an irreversible SUMO-subasumstat adduct, which prevents the transfer of SUMO from the E1 ligase complex to the E2 conjugating enzyme UBC9. This inhibition disrupts the SUMOylation pathway, a post-translational modification process often hyperactivated in various cancers to maintain cellular homeostasis and stress resilience. By blocking SUMOylation, subasumstat induces proteotoxic and genotoxic stress, leading to apoptosis in tumor cells. It is being investigated for the treatment of hematologic malignancies like multiple myeloma and non-Hodgkin lymphoma, as well as advanced solid tumors, often in combination with other therapies like proteasome inhibitors, monoclonal antibodies, or checkpoint inhibitors.

Other names

subsumstat