(E)-Necrosulfonamide ((E)-Necrosulfonamide) is an inhibitor of necroptosis. Blocks mixed lineage kinase domain-like protein (MLKL), a critical substrate of receptor-interacting serine-threonine kinase 3 (RIP3) during necrosis. Prevents MLKL-RIP1-RIP3 necrosome complex from interacting with downstream necrosis effectors. Binds and inhibits gasdermin D. Inhibits pyroptosis.

GW806742X is an inhibitor of Mixed Lineage Kinase Domain-Like protein (MLKL) which binds the MLKL pseudokinase domain (Kd: 9.3 μM) with anti-necroptosis activity. GW806742X has activity against VEGFR2.

URMC-099 is an orally bioavailable, brain penetrant MLK inhibitor (IC50: 19/42/14/150 nM, for MLK1/MLK2/MLK3/DLK), and also inhibits LRRK2 activity (IC50: 11 nM).