SZM-1209 is a potent and specific RIPK1 inhibitor with oral activity, displaying a dissociation constant (Kd) of 85 nM. It demonstrates substantial anti-necroptotic efficacy with an EC50 of 22.4 ± 8.1 nM and possesses therapeutic effects against systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI) [1].

RIPK3:>10000 nM (Kd), RIPK1:85 nM (Kd)

SZM-1209 blocks necroptotic cell death in a dose-dependent manner [1]. Specifically, SZM-1209 (0-1 μM, 6 h) inhibits the phosphorylation of the necroptosis signaling pathway involving RIPK1, RIPK3, and MLKL [1].

SZM-1209 administered at doses ranging from 25 to 100 mg/kg through oral gavage (灌胃) significantly counteracts inflammation in a systemic inflammatory response syndrome (SIRS) model induced by mTNF-α, reversing mortality in mice [1]. Additionally, when injected intraperitoneally (腹腔注射) at the same dosage, SZM-1209 markedly alleviates acute lung injury (ALI) by reducing pulmonary edema and pathological damage [1].