Table 4 GSDMD inhibitors

Necrosulfonamide (NSA)^{44,509,510,511}

~10 μM

Binding directly to Cys191 of GSDMD and inhibiting the oligomerization of GSDMD-NT

Binding to Cys86 of MLKL and blocking necroptosis

LPS-induce sepsis, AD, AS, ALF

Disulfiram (DSF).^{45,52,383,384,514,516,517,518,519}.

~10 μM

Modifying Cys191 of GSDMD and inhibiting the oligomerization of GSDMD-NT

Modifying Cys133 in the TLR-binding partner MD-2 and preventing LPS recognition;

Inhibiting NLRP3 signaling

LPS/CLP-induced sepsis, ulcerative colitis, AS, obesity and metabolic dysfunction, SARS-CoV-2 infection, ARDS, DN, NAFLD

Dimethyl fumarate (DMF)^46,409

<10 μM

Succinating Cys191 of GSDMD, blocking caspase-GSDMD interactions and inhibiting the oligomerization of GSDMD-NT

Succinating GSDME at Cys45; dopamine beta-hydroxylase; caspase-1; caspase-3

LPS-induced sepsis, FMF, EAE, HCC

Itaconate^{320,523,531,532,533}

Not known

Binding to GSDMD via Cys77 and blocking caspase-GSDMD interactions

Inhibiting NLRP3 and caspase-1

ARDS, IBD, LPS-induced sepsis

C202-2729⁵⁰³

Not known

Binding directly to the GSDMD-NT and inhibiting the oligomerization of GSDMD-NT

Not known

EAE

Caffeic acid (CA)⁵²²

Not known

Binding directly to GSDMD and blocking GSDMD cleavage

Not known

LPS-induced sepsis

GSDMD inhibitor Y1 (GI-Y1)⁴⁴⁵

Not known

Binding to GSDMD via Arg7 and inhibiting the oligomerization of GSDMD-NT

Not known

Myocardial I/R injury