GI-Y2
GI-Y2 is an orally active, selective Gasdermin D (GSDMD) inhibitor (Kd = 36.0 μM) with anti-pyroptosis activity. GI-Y2 targets GSDMD, impairs membrane anchoring of GSDMD-NT, and blocks GSDMD‑dependent lipid binding and pore formation. GI-Y2 suppresses GSDMD‑dependent pyroptosis and inflammation, mitigates atherosclerosis and cardiac injury, boosts cell survival, and reduces IL‑1β/IL‑18 secretion. GI-Y2 can be used for the research of atherosclerosis and septic myocardial injury.
For research use only. We do not sell to patients.
- CAS No.: 1008710-58-4
- Formula: C18H14N2O6S
- Molecular Weight:386.38
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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IL-18 |
IL-1β |
GI-Y2 suppresses LPS+Nigericin (HY-127019)-induced pyroptosis in PMA-differentiated THP-1 cells with an IC50 of 35.40 μM by binding to the Arg10 residue of GSDMD via hydrogen bonding to reduce GSDMD-NT membrane localization[1][2].
GI-Y2 (2.5-40 μM) directly binds to purified GST-GSDMD protein with a Kd value of 36.0 μM[1].
GI-Y2 (10 μM; 1 h) directly interacts with Flag-GSDMD expressed in HEK/293T cells, as evidenced by reduced pronase-mediated degradation of GSDMD at 10 μM[1].
GI-Y2 inhibits GSDMD-mediated pyroptosis in human AC16, HEK-293T, and HepG2 cell lines[1].
GI-Y2 (10 μM; 1 h) reduces GSDMD-N membrane binding and pyroptotic LDH release in HEK/293T cells expressing wild-type Flag-GSDMD, but not in cells expressing the GSDMDR10A mutant, confirming Arg10 as the critical binding site[1].
GI-Y2 (10-20 μM; 1 h) dose-dependently inhibits ox-LDL-induced pyroptosis in ApoE−/− mouse primary peritoneal macrophages, reducing lipid uptake, inflammatory cytokine production, and GSDMD-N activation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK/293T cells
HEK/293T cells expressing wild-type Flag-GSDMD and GSDMDR10A mutant -
Concentration:0, 10 μM
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Incubation Time:1h
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Result:Reduced pronase-mediated degradation of GSDMD at 10 μM.
Reduced GSDMD-N membrane binding and pyroptotic LDH release in HEK/293T cells expressing wild-type Flag-GSDMD, but not in cells expressing the GSDMDR10A mutant.
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Cell Line:ApoE−/− mouse primary peritoneal macrophages
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Concentration:0, 10, 20 μM
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Incubation Time:1h
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Result:Inhibits ox-LDL-induced pyroptosis.
Reduced lipid uptake, inflammatory cytokine production, and GSDMD-N activation.
GI-Y2 (10-20 mg/kg; i.g.; every 2 days; 6 weeks) dose-dependently reduces atherosclerotic plaque formation, pyroptotic inflammation, and immune cell infiltration in ApoE−/− mice fed a high-fat diet[1].
GI-Y2 (20 mg/kg; i.g.; every 2 days; 6 weeks) does not provide additional protection against atherosclerosis in Gsdmd-deficient ApoE−/− mice, confirming its effects are mediated via targeting GSDMD[1].
GI-Y2 (0.03 mg/kg; i.v.; every 3 days; 4 weeks) reduces atherosclerotic plaque formation in ApoE−/− mice, with enhanced efficacy when delivered via macrophage membrane-coated nanoparticles[1].
GI-Y2 improves survival and decreases pro-inflammatory cytokine levels in septic mice. GI-Y2 attenuates atherosclerotic lesions and septic myocardial injury by targeting GSDMD-mediated pyroptosis, and its therapeutic efficacy is significantly enhanced by macrophage membrane-coated nanoparticle delivery[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1008710-58-4
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Molecular Weight 386.38
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Formula C18H14N2O6S
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SMILES
OC(C1=CC=C(CN2C(SC(NC3=CC=C(C(O)=O)C=C3)C2=O)=O)C=C1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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