Pyroptosis Inhibitor

(E/Z)-Necrosulfonamide is a racemic compound of Necrosulfonamide (HY-100573). 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.

Azalamellarin N is an inhibitor of pyroptosis and has different inhibitory effects on different pyroptosis inducers. Azalamellarin N inhibits pyroptosis by targeting molecules that act upstream of NLRP3 inflammasome activation, rather than directly targeting components of the NLRP3 inflammasome. Inhibitory potency against different pyroptosis inducers: Nigericin (HY-127019) > R837 (HY-B0180).

Necrosulfonamide-d₄ is the deuterium labeled Necrosulfonamide (HY-100573). 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.

Acetyl zingerone is an analog of Zingerone (HY-14621). Acetyl zingerone downregulates the expression of ROS metabolism-related genes, fibroblast senescence-related genes, keratinocyte differentiation-related genes, and IL-17A target genes. Acetyl zingerone inhibits the activities of MMP-1, MMP-3, and MMP-12, as well as the activation of NLRP3 inflammasome, pyroptosis (pyroptosis), ferroptosis (ferroptosis), cartilage destruction, and UVA-induced cyclobutane pyrimidine dimer formation. Acetyl zingerone upregulates the expression of collagen, proteoglycan, extracellular matrix glycoprotein, Notch pathway, and GPX4 gene, activates Nrf2 and HO-1, induces extracellular matrix synthesis and PINK1/Parkin-mediated mitophagy (mitophagy), and promotes chondrocyte survival. Acetyl zingerone alleviates the progression of osteoarthritis in mice. Acetyl zingerone can be used in research related to skin aging, inflammatory skin diseases, osteoarthritis, melanoma, and non-melanoma skin cancer.

Kanglexin is an orally active and novel anthraquinone compound. Kanglexin inhibits NLRP3 inflammatory body activation and cell pyroptosis, and has a cardioprotective effect. Kanglexin promotes angiogenesis through FGFR1/ERK signaling pathway and accelerates diabetic wound healing. In addition, Kanglexin has the effect of lipid-lowering and inhibiting the dedifferentiation of vascular smooth muscle cells, and can be used in the study of hyperlipidemia, fatty liver and atherosclerosis.

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.

Antcin A is an orally active modulator of p53 and glucocorticoid receptor (GR), with an IC₅₀ of 8.55 μM against human GR. Through transcriptional activation of p53, Antcin A induces miR-200c and inhibits ZEB1, regulates epithelial-mesenchymal transition markers, and suppresses cancer cell migration/invasion. Antcin A activates GR, inhibits Na⁺/K⁺-ATPase and NLRP3 inflammasome assembly, pyroptosis (pyroptosis) and pro-inflammatory cytokine release, reduces hepatic lipid deposition, improves liver function, and reverses metabolic changes induced by the SARS-CoV-2 spike protein. Antcin A can be used in research related to breast cancer, head and neck cancer, non-alcoholic fatty liver disease, and coronavirus disease 2019 (COVID-19).

Aureusidin is a flavonoid compound that is isolated and extracted from Antirrhinum majus and exhibits oral activity. Aureusidin possesses antioxidant, neuroprotective, and anti-inflammatory properties. Aureusidin directly targets and binds MD2 and Caspase-3 with high affinity, synergistically inhibits the TLR4/NF-κB inflammatory pathway and GSDME-mediated pyroptosis, and activates the Nrf2/HO-1 antioxidant axis via the ROS/MAPKs pathway. Aureusidin is a bovine liver arginase inhibitor with an IC₅₀ of 57.1 µM. Aureusidin is used for research on inflammation-related diseases (osteoarthritis), acute liver injury, and endothelial dysfunction.

Relaxin H3 (human) TFA is a relaxin peptide with anti-inflammatory, anti-apoptotic, anti-pyroptotic, anti-migratory, protective and anti-fibrotic activities. Relaxin H3 (human) TFA acts on RXFP1 to generate cAMP and reduce the levels of ATP and ROS. Relaxin H3 (human) TFA inhibits renal inflammatory pyroptosis (pyroptosis), NLRP3 inflammasome activation, caspase-1 activation, IL-1β/IL-18 secretion, collagen synthesis, TGF-β1 signaling pathway, Smad2 phosphorylation, myofibroblast differentiation, TIMP expression, and HRMEC migration. Relaxin H3 (human) TFA activates AMPK, upregulates MFN2 expression, improves mitochondrial quality control and membrane potential, inhibits apoptosis (apoptosis) and pyroptosis, restores retinal ultrastructure, and reverses excessive left ventricular collagen expression. Relaxin H3 (human) TFA can be used in studies related to kidney stones, nephrocalcinosis, diabetic cardiomyopathy, fibrotic cardiomyopathy, and diabetic retinopathy.

Lenalidomide-d₅ (CC-5013-d₅) is the d₅-labeled Lenalidomide (HY-A0003). Lenalidomide (CC-5013) is an orally active immunomodulatory agent that binds CRBN as a molecular glue to alter substrate specificity, inducing ubiquitination and proteasome-dependent degradation of IKZF1, IKZF3 and CK1α. Lenalidomide induces apoptosis by degrading IKZF1/3, and activates p53 by degrading CK1α. Lenalidomide promotes IL-2 release and effector functions of CD8⁺ T/NK cells, while inhibiting TNF-α secretion and M1-type pyroptosis. Lenalidomide can be used in research related to hematological malignancies, acute liver failure and acute kidney injury.

7DG (7-Desacetoxy-6,7-dehydrogedunin) is a PKR inhibitor, P2X7 purinergic receptor inhibitor, and skin-lightening agent. 7DG binds outside the ATP-catalytic domain of PKR, blocks the kinase activity-independent protein-protein interactions of PKR, inhibits the phosphorylation and activity of PKR, disrupts ASC assembly and caspase-1 activation, and suppresses the activation of the NLRP1 inflammasome. 7DG inhibits pyroptosis, suppresses the ATP-P2X7 signaling pathway, and abolishes ATP-induced increases in the expression levels of MITF, tyrosinase, PMEL/gp100, and melanin content. 7DG exerts skin-lightening effects in cultured skin in vitro. 7DG can be used in research related to chronic obstructive pulmonary disease, gout, type 2 diabetes, Alzheimer's disease, and hyperpigmentary skin disorders.

GI-Y2 is an orally active, selective Gasdermin D (GSDMD) inhibitor (K_d = 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.

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.

Garcinoic acid is an orally active anti-inflammatory agent that crosses the blood-brain barrier. Garcinoic acid also enhances efferocytosis and enzyme/receptor regulation, and selectively inhibits human COX-2, porcine α-amylase, Saccharomyces cerevisiae α-glucosidase and human DNA polymerase β (IC₅₀=11 μM), as well as activates human PXR. Garcinoic acid enhances macrophage efferocytosis via receptors such as MerTK and LRP-1, and promotes the production of pro-resolving lipid mediators. Garcinoic acid inhibits NF-κB activation and pro-inflammatory cytokine secretion, interferes with Aβ aggregation, downregulates NLRP3 inflammasome activity, and binds to targets including CD44 and EGFR to inhibit leukemia cell proliferation. The pharmacological activities of Garcinoic acid, such as antioxidant, anti-inflammatory and lipid metabolism-regulating effects, are widely used in studies related to various diseases including atherosclerosis, Alzheimer's disease, type 2 diabetes, inflammatory bowel disease and viral pneumonia.

(-)-Aspartic acid (Standard) is the analytical standard of (-)-Aspartic acid. This product is intended for research and analytical applications. (-)-Aspartic acid is a pyroptosis inhibitor. (-)-Aspartic acid acts as a neurotransmitter and neuromodulator, participates in hormone synthesis and regulation, and plays a role in nervous system development and endocrine system.

Lenalidomide hydrochloride (CC-5013 hydrochloride) is an orally active immunomodulatory agent that binds CRBN as a molecular glue to alter substrate specificity, inducing ubiquitination and proteasome-dependent degradation of IKZF1, IKZF3 and CK1α. Lenalidomide hydrochloride induces apoptosis by degrading IKZF1/3, and activates p53 by degrading CK1α. Lenalidomide hydrochloride promotes IL-2 release and effector functions of CD8⁺ T/NK cells, while inhibiting TNF-α secretion and M1-type pyroptosis. Lenalidomide hydrochloride can be used in research related to hematological malignancies, acute liver failure and acute kidney injury.

ACT001 (Dimethylaminomicheliolide; DMAMCL) hydrochloride is an orally active, blood-brain barrier-permeable anti-inflammatory and anti-tumor agent. ACT001 hydrochloride exerts microglia-mediated neuroanti-inflammatory effects by inhibiting the AKT/NF-κB/NLRP3 axis and suppressing apoptosis (apoptosis). ACT001 hydrochloride inhibits tumor proliferation by upregulating NKTR and inhibiting AKT. ACT001 hydrochloride alleviates metabolic-associated fatty liver disease by regulating gut microbiota and inhibiting ileal FXR. ACT001 hydrochloride inhibits pyroptosis (pyroptosis) and pro-inflammatory cytokine release by activating PPAR-γ and inhibiting NF-κB/NLRP3.

NLRP3-IN-83 is a selective and orally active NLRP3 inflammasome activation inhibitor. NLRP3-IN-83 exhibits good inhibitory IL-1β activity with an IC₅₀ of 1.4 μM by blocking NLRP3, independent of NF-κB signaling. NLRP3-IN-83 only slightly inhibits AIM2 inflammasome pathway, but has no effect on NLRC4 inflammasome. NLRP3-IN-83 prevent cell pyroptosis and exhibits significant anti-inflammatory efficacy in ulcerative colitis model. NLRP3-IN-83 can be used for the study of inflammatory bowel disease (IBD).

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.

NLRP3-IN-55 (Compound 19) is a potent NLRP3 inhibitor (IC₅₀ = 0.34 μM). NLRP3-IN-55 directly targets the NLRP3 protein (K_D = 0.45 μM), blocking the assembly and activation of the NLRP3 inflammasome, leading to anti-inflammatory effects and inhibition of cellular pyroptosis.