GSDMD agonist DMB is a direct and selective gasdermin D (GSDMD) agonist, activates GSDMD pore formation to trigger liposome leakage with EC50 of 0.7 uM, activates GSDMD pore formation and pyroptosis without cleaving GSDMD.
DMB directly binds to GSDMD by microscale thermophoresis (MST) with a dissociation constant (KD) of 1.1 uM.
DMB induces pyroptosis in immortalized and primary cells in a GSDMD-dependent and cleavage-independent manner.
DMB binds to GSDMD and induces cleavage-independent GSDMD oligomerization and pore formation. activated human GSDMD but not other human gasdermins, also activates mouse GSDMD in the liposome leakage assay, albeit with ∼5-fold reduced efficacy.
GSDMD agonist DMB modifies GSDMD at C191, which is conserved in GSDMD from different species but not in other gasdermin family members.
DMB induces tumor regression and enhances antitumor immunity that depends on GSDMD expression in the tumor.