Pyroptosis

2-Bromohexadecanoic acid (2-BP) is a non-metabolizable palmitate analog, an agonist of PPARδ, which acts as a palmitoylation inhibitor and inhibits DHHC-mediated palmitoylation.

Ac-FLTD-CMK is an inhibitor derived from abscisicin D (GSDMDD) with specific inhibitory effects on inflammatory caspases. ac-FLTD-CMK showed inhibitory effects on caspases-1, caspases-4 and caspases-11 with IC50s of 46.7 nM, 1.49 μM and 329 nM, respectively. Ac-FLTD-CMK showed potency against caspases-1, caspases-4 and caspases-11, but not against apoptosis-associated caspase-3.

Disulfiram (TETD) is an inhibitor of the acetaldehyde dehydrogenase ALDH, inhibiting hALDH1 and hALDH2 (IC50=0.15/1.45 μM) with specificity. Disulfiram is acutely sensitized to alcohol and also inhibits GSDMD pore formation.

LDC7559 inhibits gasdermin D (GSDMD) by blocking neutrophil extracellular trap (NET) at late stage.

Punicalin exerts anti-inflammatory, antioxidative, and anti-hepatotoxic activities, it shows inhibitory activity on HIV-1 reverse transcriptase in a dose-dependent manner, with an IC50 of 0.11 microg ml (0.14 microM).

Ac-YVAD-CMK (Ac-Tyr-Val-Ala-Asp-CMK) is a selective and irreversible inhibitor of Caspase-1 and inhibits pyroptosis, IL-1β and IL-18. Ac-YVAD-CMK shows neuroprotective and anti-inflammatory capacity.

antcin A is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom Antrodia cinnamomea with strong anti-inflammatory and anti-tumor effects.

Nigericin is a polyether antibiotic with potent antimicrobial, antimalarial, anticoronaviral and anticancer activities. It is capable of promoting cellular potassium efflux, inducing Caspase-1/GSDMD and Caspase-3-mediated cellular pyroptosis and apoptosis in triple-negative breast cancer, and inducing apoptosis in PEL (primary exudative lymphoma) cells through mitochondrial dysfunction and Wnt/β-catenin signaling downregulation.

Apilimod 2HCl (STA 5326 2HCl) is a PIKFYVE kinase inhibitor that promotes NLRP3 inflammatory vesicle activation, IL-1β secretion, and cellular pyroptosis, and is used in the study of amyotrophic lateral sclerosis.

1. Polyphyllin VI has hemostasis , expectorant , bacteriostasis, anticytotoxic, anti pregnancy kill sperm effects.

Calenduloside E (Silphioside F) exhibits hypoglycemic activities by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine in oral glucose-loaded rats.

1,7-Diphenyl-4-hepten-3-one is a compound isolated from Alpinia officinarum, which activates the Nrf2 pathway to suppress pyroptosis. It alleviates cognitive impairment and pathological damage in APP/PS1 mice and prevents oxidative stress damage while reducing levels of pyroptosis-related proteins. 1,7-Diphenyl-4-hepten-3-one enhances Aβ-induced proliferation in HT22 cells and can be used in Alzheimer’s disease research.

Sodium metatungstate (Sodium polyoxotungstate) is a potent inhibitor of ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), with Ki values of 2.58 μM for NTPDase 1, 3.26 μM for NTPDase 3, and 28.8 μM for NTPDase 2.

INF 195 is an inflammasome NLRP3 inhibitor that inhibits NLRP3-driven macrophage pyroptosis and IL-1β release. INF 195 reduces isoproterenol-induced hypertrophy in H9c2 rat myoblasts and can be used to study myocardial ischemia and myocardial infarction.

NLRP3 AIM2-IN-3 is a unique molecule that inhibits NLRP3 and AIM2 inflammasome activation in a species-specific manner. It has an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3 AIM2-IN-3 is a potent inhibitor of NLRP3 and AIM2 inflammasome-dependent cell lysis with an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3 AIM2-IN-3 inhibits LPS nigericin NLRP3 AIM2-IN-3 inhibits LPS nigericin-stimulated cell lysis in THP-1 macrophages with an IC50 value of 0.077 ± 0.008 μM. NLRP3 AIM2-IN-3 interferes with the interaction of NLRP3 or AIM2 with the bridging protein ASC, inhibiting oligomerization of ASC.

(-)-Aspartic acid (L-Homoproline) is an endogenous amino acid existing in invertebrates and vertebrates. It can regulate testosterone synthesis and is an agonist of NMDA receptor.

Morroniside would act as a regulator of hepatic inflammatory reactions and lipid metabolism in db db mice. It exhibits protective effects against diabetic renal damage and human umbilical vein endothelial cells, by inhibiting hyperglycemia and oxidative s

Ac-FEID-CMK TFA is a selective zebrafish GSDMEb-derived peptide inhibitor that reduces mortality and renal injury in infectious shock. It inhibits pyroptosis in vivo, attenuates septic AKI (acute kidney injury), and inhibits the caspy2-mediated atypical inflammatory vesicle pathway.

Britannin, a sesquiterpene lactone, inhibits proliferation and induces apoptosis through the mitochondrial signaling pathway in human breast cancer cells.

Triclabendazole (CGA89317) has been used in trials studying Parasitic Disease.

Ethyl pyruvate is a simple aliphatic ester of pyruvic acid and has been shown to have robust neuroprotective effects via its anti-inflammatory, anti-oxidative, and anti-apoptotic functions.

GI-Y2 is a GSDMD inhibitor that suppresses macrophage pyroptosis induced by oxidized low-density lipoprotein (ox-LDL). In vivo, GI-Y2 dose-dependently reduces atherosclerotic plaques and decreases lesion size and fibrosis in the aortic root of ApoE-/- mice. GI-Y2 holds potential for research in pyroptosis and cardiovascular diseases, such as atherosclerosis.

NLRP3-IN-78 (compound 21) is an NLRP3 inhibitor with a 46.72% inhibition rate of GSDMD-induced pyroptosis at 5 μM. It binds to the NLRP3 protein and prevents GSDMD-NT oligomerization. Additionally, NLRP3-IN-78 inhibits GSDMD cleavage and upstream NF-κB signaling, demonstrating anti-inflammatory activity.

INF200 (compound 5), a sulfonylurea-based inhibitor of NLRP3 and associated pyroptosis, exhibits cardiometabolic benefits in a rat model of high-fat diet (HFD)-induced metaflammation and demonstrates anti-inflammatory effects by reducing IL-1β release in human macrophages at a concentration of 10 μM. Additionally, it enhances glucose and lipid profiles, diminishes systemic inflammation and cardiac dysfunction biomarkers, notably BNP, and ameliorates myocardial damage linked to ischemia reperfusion injury (IRI) as assessed by hemodynamic parameters [1].