Necroptosis

Necroptosis is a form of regulated necrotic cell death mediated by receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. Necroptosis is characterized by early loss of plasma membrane integrity, leakage of intracellular contents, and organelle swelling. The cells dying through necroptosis lack the typical apoptotic characteristics, such as membrane blebbing, chromatin condensation, and intranucleosomal DNA cleavage into 180 bp DNA laddering, but may show TUNEL positivity.

Necroptosis triggers innate immune responses by rupturing dead cells and releasing intracellular components, it can be caused by Toll-like receptor (TLR)-3 and TLR-4 agonists, tumor necrosis factor (TNF), certain microbial infections, and T cell receptors. Necroptosis signaling is modulated by receptor-interacting protein kinase (RIPK) 1 when the activity of caspase-8 becomes compromised. Activated death receptors (DRs) cause the activation of receptor-interacting serine-threonine kinase 1 (RIPK1) and the RIPK1 kinase activity-dependent formation of an RIPK1-RIPK3-MLKL, which is complex II. RIPK3 phosphorylates MLKL, ultimately leading to necrosis through plasma membrane disruption and cell lysis.

Necroptosis Related Products (71):

By Effects:	Inhibitors (30) Activators (3) Inducers (32)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-14909

Bardoxolone	Inhibitor	99.14%
Bardoxolone (RTA 401; CDDO) is a novel nuclear regulatory factor (NRf-2) activator. Bardoxolone is a potent necroptosis inhibitor that inhibits Z-VAD-FMK-induced necroptosis. Bardoxolone methyl enhances the antioxidant system, modulates inflammatory cytokines and inhibits apoptosis in rat kidney, demonstrating inhibition on APAP-induced acute kidney injury (AKI) and analgesic effect. Additionally, Bardoxolone methyl decreases Paclitaxel (PAC) (HY-B0015)-induced mitochondrial damage in neuronal cells. Bardoxolone methyl is promising for the research of chemotherapy-induced neuropathic pain and chronic kidney disease.

HY-Y0698

Thioacetamide		≥98.0%
Thioacetamide (TAA) is an indirect hepatotoxin and causes parenchymal cell necrosis. Thioacetamide requires metabolic activation by microsomal CYP2E1 to thioacetamide-S-oxide initially and then to thioacetamide-S-dioxide, which is a highly reactive metabolite, and its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Thioacetamide can induce chronic liver fibrosis, encephalopathy and other events model.

HY-B1218

Sulfaphenazole	Inhibitor	99.83%
Sulfaphenazole is a selective inhibitor of human cytochrome P450 (CYP) 2C9 enzyme. Sulfaphenazole is a cytoprotective agent against light-induced death of photoreceptors. Sulfaphenazole inhibits light-induced necrosis and mitochondrial stress-initiated apoptosis. Sulfaphenazole is an off patent sulfonamide antibiotic and demonstrates bactericidal activity through enhanced M1 macrophage activity. Sulfaphenazole can significantly reduce infarct size and restore post-ischemic coronary flow following ischemia and reperfusion.

HY-144828

RIP1/RIP3/MLKL activator 1	Inducer
RIP1/RIP3/MLKL activator 1 (Compound 6i) is a potent anti-glioma agent. RIP1/RIP3/MLKL activator 1 induces necroptosis through RIP1/RIP3/MLKL pathway. RIP1/RIP3/MLKL activator 1 exerts acceptable BBB permeability.

HY-B0863

Glyphosate	Inducer	≥98.0%
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is an herbicidal derivative of the amino acid glycine. Glyphosate inhibits the enzymatic activity of the 5-endopyruvylshikimate 3-phosphate synthase (EPSPS) in the shikimic acid pathway, preventing the synthesis of the aromatic amino acids tyrosine, phenylalanine, and tryptophan. Glyphosate induces oxidative stress, neuroinflammation, and mitochondrial dysfunction, processes that lead to neuronal death by autophagia, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders.

HY-158312

UH15-38	Inhibitor	99.80%
UH15-38 is a potent RIPK3 inhibitor with an IC₅₀ value of 20 nM. UH15-38 blocks IAV (influenza A virus)-activated necroptosis. UH15-38 dampens IAV-induced lung injury.

HY-P2780A

Cathepsin B, Human Liver
Cathepsin B, Human Liver is a cysteine protease in liver and is involved in multiple kinds of programmed cell death (including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death). Cathepsin B (CTSB) have been implicated in various ECM-related disorders, such as dilated cardiomyopathy, lung fibrosis, proteinuric renal disorders, cancer, and osteoporosis.

HY-106777

Cyclopentenylcytosine	Inducer	99.76%
Cyclopentenylcytosine (CPC) is a nucleoside analog that reduces the levels of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells by inhibiting CTP synthetase. Cyclopentenylcytosine also promotes the phosphorylation of 1-β-D-arabinorubosylmannosylcytidine (araC) and its DNA intercalation activity. Cyclopentenylcytosine induces apoptosis and necrosis in the human T lymphocyte line MOLT-3 in a concentration (50-300 nM) and time (8-16 h) dependent manner. Co-treatment of cyclopentenylcytosine with araC enhances the effects of induction of apoptosis and necrosis, as well as its cytotoxicity in T lymphoblasts.

HY-W010800

Cholesteryl hemisuccinate	Inhibitor	99.70%
Cholesteryl hemisuccinate is a with hepatoprotective an anticancer activity. Cholesteryl hemisuccinate inhibits Acetaminophen (AAP, HY-66005) hepatotoxicity, and prevents AAP-induced hepatic apoptosis and necrosis. Cholesteryl hemisuccinate inhibits DNA polymerase and DNA topoisomerase to inhibit DNA replication and repair and cell division. Thus, Cholesteryl hemisuccinate inhibits tumor growth.

HY-134050

Apostatin-1	Inhibitor	99.24%
Apostatin-1 (Apt-1) is a potent TRADD inhibitor. Apostatin-1 can bind with TRADD-N (K_D=2.17 μM), disrupting its binding to both TRADD-C and TRAF2. Apostatin-1 modulates the ubiquitination of RIPK1 and beclin 1. Apostatin-1 blocks apoptosis and restores cellular homeostasis by activating autophagy in cells with accumulated mutant tau, α-synuclein, or huntingtin.

HY-N0244

Theaflavin-3'-gallate	Inhibitor	98.68%
Theaflavin-3'-gallate is a monomer of theaflavins found in black tea, which has anti-UVB damage activity and inhibits cell apoptosis and necroptosis. Theaflavin-3'-gallate acts as a pro-oxidant and induces oxidative stress in cancer cells, inhibiting xanthine oxidase (OX), with an IC₅₀ of 7.6 μM.

HY-W010201

Citronellol	Inducer	98.60%
Citronellol ((±)-Citronellol) is an orally active inducer of apoptosis. Citronellol can prevent oxidative stress, mitochondrial dysfunction, and apoptosis in the SH-SY5Y cell Parkinson's disease model induced by 6-OHDA by regulating the ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways. Citronellol can induce necroptosis in human lung cancer cells through the TNF-α pathway and accumulation of ROS. Citronellol can reduce the levels of LC-3 and p62 to regulate the autophagy pathway, inhibit oxidative stress and neuroinflammation, and thus have neuroprotective effects on Parkinson's rats. Citronellol exhibits anti-fungal activity against Trichophyton rubrum by inhibiting ergosterol synthesis.

HY-B0608

Chlorhexidine (digluconate)	Inducer	99.45%
Chlorhexidine digluconate is a chlorophenyl biguanide with broad antibacterial action against both Gram (+) and (-) bacteria and fungi. Chlorhexidine digluconate is a broad-spectrum antiseptic and disinfectant. Chlorhexidine digluconate is effective to prevent and control infectious diseases of the mouth by killing bacteria in saliva and tongue. Chlorhexidine digluconate is a cytotoxic agent and induces cell necrosis and apoptosis.

HY-108351

IM-54		99.31%
IM-54 is a selective inhibitor of oxidative stress-induced necrosis. IM-54 shows potent inhibitory activity against H₂O₂-induced necrosis. IM-54 acts as a potential cardioprotective agent and biological tool for investigating the molecular mechanisms of cell death.

HY-12456

Duocarmycin SA	Inducer	99.55%
Duocarmycin SA is an orally active antitumor antibiotic with an IC₅₀ of 10 pM. Duocarmycin SA is an extremely potent cytotoxic agent capable of inducing a sequence-selective alkylation of duplex DNA. Duocarmycin SA demonstrates synergistic cytotoxicity against glioblastoma multiforme (GBM) cells treated with proton radiation in vitro.

HY-117200

Necrostatin-7	Inhibitor	≥98.0%
Necrotatin-7 (Nec-7) is a potent necroptosis inhibitor with an EC₅₀ of 10.6 μM. Necrotatin-7 does not inhibit recombinant RIP1 kinase.

HY-124546

Necrostatin-5	Inhibitor	98.43%
Necrostatin-5 (Nec-5) is a potent necroptosis inhibitor with an EC₅₀ value of 0.24 µM. Necrostatin-5 also is a RIP1 inhibitor. Necrostatin-5 shows cardioprotective effects.

HY-135826

Necroptosis-IN-1	Inhibitor	98.39%
Necroptosis-IN-1, an analog of Necrostatin-1, is a potent necroptosis inhibitor. Necroptosis-IN-1 is a RIPK inhibitor.

HY-P2780

Cathepsin B, Bovine spleen
Cathepsin B, Bovine spleen is a cysteine protease and is involved in multiple kinds of programmed cell death (including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death).

HY-122912

ALDH1A inhibitor 673A	Inducer	98.81%
ALDH1A inhibitor 673A is an ALDH1A inhibitor. ALDH1A inhibitor 673A inhibits all three ALDH1A family members (IC₅₀: 246 nM, 230 nM, 348 nM for ALDH1A1, ALDH1A2, ALDH1A3 respectively. ALDH1A inhibitor 673A induces necroptotic cell death preferentially in CD133+ ovarian CSCs. ALDH1A inhibitor 673A also inhibits chemotherapy-resistant tumor growth.

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