SCR-1481B1

SCR-1481B1 (Metatinib anhydrous; c-Met inhibitor 2) is an inhibitor of the N-terminal fragment of Gasdermin D (GSDMD), with an IC₅₀ of 1.04 μM and a K_a of 0.42 μM in mice. SCR-1481B1 effectively blocks GSDMD-NT oligomerization and pore formation, inhibits GSDMD-mediated pyroptosis (Pyroptosis), preserves mitochondrial integrity, and reduces proinflammatory cytokine secretion. SCR-1481B1 also inhibits angiogenesis, exerts GSDMD-independent antitumor effects, and enhances the infiltration of antitumor immune cells. SCR-1481B1 is also an inhibitor targeting to c-MET and VEGFR2, can be used in studies related to melanoma and sepsis^[1][2][3][4]. IC50 & Target:c-Met, VEGFR In Vitro:SCR-1481B1 (1-40 μM; 1 h pre-incubation) dose-dependently inhibits LPS plus nigericin-induced GSDMD-mediated pyroptosis in iBMDMs, reducing both LDH release and IL-1^β secretion^[1].
SCR-1481B1 (20 μM) inhibits LPS plus nigericin-induced GSDMD-mediated pyroptosis in human THP-1 monocytes, reducing both LDH release and IL-1β secretion^[1].
SCR-1481B1 (20 μM; 4 h) inhibits mouse and human GSDMD-N oligomerization and subsequent pyroptotic cell death in HEK293T cells^[1].
SCR-1481B1 (20 μM; 4 h) inhibits GSDMD oligomerization and pyroptotic cell death downstream of caspase-1/11-mediated GSDMD cleavage in HEK293T cells^[1].
SCR-1481B1 (20 μM) inhibits human and mouse GSDMD-N oligomerization in the cytosol of HEK293T cells, as measured by split-luciferase reconstitution^[1].
SCR-1481B1 (20 μM; 4 h pre-incubation) specifically binds to core sites at the oligomerization interface I of mouse GSDMD-N, enhancing its stability against protease degradation^[1].
SCR-1481B1 (20 μM) directly binds to core sites at the oligomerization interface I of purified mouse GSDMD-N, increasing its thermal stability^[1].
SCR-1481B1 (0.15-20 μM; 60 min) inhibits GSDMD-N-mediated liposome pore formation with an IC₅₀ of 1.04 μM^[1].
SCR-1481B1 (Metatinib) binds to the GSDMD dimer with a docking score of -7.28 kcal/mol^[3]. In Vivo:SCR-1481B1 (10 mg/kg; i.p.; single dose; administered 4 hours prior to LPS challenge) reduces LPS-induced sepsis mortality to ~20% and lowers serum inflammatory cytokine levels in wild-type mice by targeting GSDMD^[1].
SCR-1481B1 (10 mg/kg; i.p.; single dose) improves survival and reduces serum inflammatory cytokine levels in E. coli-induced septic mice, though it does not significantly reduce organ bacterial burden^[1].
SCR-1481B1 (10 mg/kg; i.p.; every other day; starting after tumor implantation) enhances the antitumor efficacy of anti-PD-L1 antibody in a B16F10 melanoma model by increasing tumor-infiltrating immune cells and reducing T cell exhaustion, with activity independent of GSDMD^[1].