Pyroptosis Inhibitor

Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram, a copper ion carrier, with Cu²⁺ increases intracellular ROS levels and induces cuproptosis.

2-Bromohexadecanoic acid (2-Bromopalmitate; 2-BP) is a palmitoylation inhibitor targeting DHHC (Asp-His-His-Cys) protein palmitoyltransferase. 2-Bromohexadecanoic acid inhibits palmitoylation of GSDME-C during pyroptosis and inhibits BAK/BAX-Caspase 3-GSDME pathway-mediated pyroptosis.

SK56 is a GSDMD-NT pore inhibitor. SK56 inhibits pyroptosis (Pyroptosis) and the release of pyroptosis-related cytokines in macrophages and human peripheral blood leukocytes. SK56 prevents extensive cell death in human alveolar organoids in an organoid-macrophage co-culture model. SK56 prevents death from infectious shock induced by LPS (HY-D1056) or cecal ligation and puncture in mice. SK56 can be used in studies related to sepsis.

7-Oxogedunin (Compound 7DG; Compound 16) is a small molecule that protects macrophages from cell pyroptosis induced by anthrax lethal toxin (LT). Its target is protein kinase R (PKR). 7-Oxogedunin can widely inhibit the assembly of various inflammasomes (NLRP1 and NLRP3) and the activation of caspase-1 by inhibiting the kinase-independent function of PKR. 7-Oxogedunin has growth inhibitory activity on European corn borer larvae. 7-Oxogedunin can be used for LT toxicity inhibition and pest control research.

Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Inclisiran sodium is a double-stranded small interfering RNA (siRNA) molecule. Inclisiran sodium inhibits the transcription of PCSK9. Inclisiran sodium inhibits Pyroptosis, activates PPARγ, and reduces NLRP3, cleaved caspase-1, IL-1β, and IL-18. Inclisiran sodium has anti-inflammatory, lipid-regulating and anti-atherosclerotic activities. Inclisiran sodium can be used in researches of hyperlipidemia and cardiovascular disease (CVD).

LDC7559 is a gasdermin D (GSDMD) inhibitor via blocking neutrophil extracellular trap (NET) in the late stages .

NLRP3/AIM2-IN-3 (compound 59) is a potent inhibitor with differential species specific effects against NLRP3 and AIM2 inflammasome-dependent pyroptosis. NLRP3/AIM2-IN-3 shows inhibitory efficacy against pyroptosis in THP-1 macrophages stimulated with LPS/nigericin, with an IC₅₀ of 0.077 ± 0.008 μM. NLRP3/AIM2-IN-3 disturbs the interaction of NLRP3 or AIM2 with the adaptor protein ASC and inhibited ASC oligomerization.

Inclisiran is a double-stranded small interfering RNA (siRNA) molecule. Inclisiran inhibits the transcription of PCSK9. Inclisiran inhibits Pyroptosis, activates PPARγ, and reduces NLRP3, cleaved caspase-1, IL-1β, and IL-18. Inclisiran has anti-inflammatory, lipid-regulating and anti-atherosclerotic activities. Inclisiran can be used in researches of hyperlipidemia and cardiovascular disease (CVD).

IRF1-IN-1 (Compound I-2) is an IRF1 inhibitor. IRF1-IN-1 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-1 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1). IRF1-IN-1 has a protective effect on ionizing radiation-induced inflammatory skin injury.

ODN TTAGGG (ODN A151), an inhibitory oligonucleotide (ODN), is a TLR9, AIM2, and cGAS antagonist. ODN TTAGGG inhibits AIM2 inflammasome activation and cGAS activation through competition with DNA. ODN TTAGGG blocks AIM2-mediated Pyroptosis and inhibits IL-18 production. ODN TTAGGG has immunosuppressive effects and can be used in research on related autoimmune diseases such as lupus erythematosus. ODN TTAGGG sequence: 5'-T-T-A-G-G-G-T-T-A-G-G-G-T-T-A-G-G-G-T-T-A-G-G-G-3'.

Ethyl pyruvate is a simple derivative of the endogenous metabolite pyruvate. Ethyl pyruvate is an HMGB1 release inhibitor. Ethyl pyruvate can induce apoptosis by autophagy. Ethyl pyruvate has anti-inflammatory, antioxidant and anti-tumor activity. Ethyl pyruvate can be used in the study of neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Britannin is an NLRP3 inhibitor with an IC₅₀ of 3.630 μM, exhibiting anti-inflammatory activity. Britannin inhibits the activation and assembly of the NLRP3 inflammasome by blocking the interaction between NLRP3 and NEK7. Additionally, Britannin demonstrates antitumor activity by inhibiting the proliferation of tumor cells through blocking the interaction between HIF-1α and Myc, thereby suppressing PD-L1 expression and enhancing cytotoxic T lymphocyte activity. Britannin can also induce apoptosis and autophagy in liver cancer cells by activating ROS-regulated AMPK. Britannin holds promise for research in the fields of anti-inflammatory and antitumor therapeutics.

Disulfiram (Standard) is the analytical standard of Disulfiram. This product is intended for research and analytical applications. Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram + Cu²⁺ increases intracellular ROS levels triggering apoptosis of ovarian cancer stem cells^[1-6].

Sweroside is an iridoid glycoside that targets multiple targets, including the Keap1/Nrf2 axis, NLRP3 inflammasome, SIRT1, NF-κB, AMPK/mTOR pathway, and caspase family. Sweroside promotes Nrf2 nuclear translocation by competitively binding to Keap1. Sweroside also inhibits oxidative stress and NLRP3-mediated pyroptosis by activating Nrf2, inhibits NF-κB inflammatory pathway by activating SIRT1, and promotes autophagy and induces caspase-dependent apoptosis via the AMPK/mTOR pathway. Sweroside has antioxidant, anti-inflammatory, anti-apoptotic, and lipid metabolism regulating activities, and can be used in the research of myocardial ischemia-reperfusion injury, leukemia, acute lung injury, non-alcoholic fatty liver disease, and other fields.

Periplogenin is an orally active cardiac glycoside found in Cortex periplocae. Periplogenin can induce ROS production and necroptosis and cause G0/G1 phase arrest. Periplogenin can inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD signaling. Periplogenin suppresses growth of prostate carcinoma cells by docking to an ATP1A1 protein pocket and forming a hydrogen bond with T804. Periplogenin can be used for the researches of cancer, inflammation and immunology, such as prostate carcinoma, rheumatoid arthritis and psoriasis.

RG100204 is a selective, orally available inhibitor of the aquaporin AQP9. RG100204 directly inhibits AQP9 channel function, preventing the transmembrane transport of water, glycerol, and H²O². RG100204 reduces the activation of the NLRP3 inflammasome and p38 MAPK signaling pathways, thereby alleviating inflammation and pyroptosis. RG100204 reduces multi-organ dysfunction in a mouse sepsis model and shows glucose-regulating effects in diabetic db/db mice.

Ac-FLTD-CMK, a gasdermin D (GSDMD)-derived inhibitor, is a specific inflammatory caspases inhibitor. Ac-FLTD-CMK is effective against caspases-1 (IC₅₀ of 46.7 nM), caspases-4 (IC₅₀ of 1.49 μM), caspases-5 (IC₅₀ of 329 nM), and caspases-11 , but not the apoptotic caspases such as caspase-3.

IRF1-IN-2 (Compound I-19) is an IRF1 inhibitor. IRF1-IN-2 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-2 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1; inhibits the Pho of TKB1, upregulates GPX4 and downregulates FACL4). IRF1-IN-2 has a protective effect on ionizing radiation-induced inflammatory skin injury.

Morroniside has neuroprotective effect by inhibiting neuron apoptosis and MMP2/9 expression.