1. Signaling Pathways
  2. Apoptosis
  3. 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 (32):

Cat. No. Product Name Effect Purity
  • HY-144828
    RIP1/RIP3/MLKL activator 1
    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-134050
    Inhibitor 99.24%
    Apostatin-1 (Apt-1) is a potent TRADD inhibitor. Apostatin-1 can bind with TRADD-N (KD=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-Y0698
    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-108351
    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-W010800
    Cholesteryl hemisuccinate
    Inhibitor ≥98.0%
    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-153435
    RIP1 kinase inhibitor 5
    RIP1 kinase inhibitor 5 (example 1) is a potent inhibitor of RIP1, which is used as a checkpoint kinase to control tumor immunity. RIP1 kinase inhibitor 5 is similar with SIR1-365 (compound 13), which inhibits necrosis and iron death activity.
  • HY-149407
    Multi-kinase-IN-4 (compound 5d) is multi-targeted kinase inhibitor, including VEGFR2, EGFR, HER2, and CDK2, with IC50 values of 0.33, 0.22, 0.18 and 2.09 μM, respectively. Multi-kinase-IN-4 shows broad-spectrum anti-cancer activities against HepG2, MCF-7, MDA-231, and HeLa cell lines (IC50 = 1.94–7.1 µM), but exhibits lower toxicity in the WI-38 cells (IC50 = 40.85 µM). Multi-kinase-IN-4 induces apoptosis and arrests cell cycle at S phase in HepG2 cells. Multi-kinase-IN-4 has the potential for the research of cancer.
  • HY-116107
    AG311 is an anticancer and antimetastatic agent. AG311 induces rapid necrosis in numerous cancer cell lines.
  • HY-117200
    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-12456
    Duocarmycin SA
    Inducer ≥98.0%
    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-124546
    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-N3417
    Kongensin A
    Inhibitor ≥98.0%
    Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications.
  • HY-148454
    Inhibitor 99.77%
    Necroptosis-IN-3 (Compound 69) is a necroptosis inhibitor that inhibits TNF-α induced necroptosis. Necroptosis-IN-3 (Compound STX1638) also inhibits 11β-HSD1.
  • HY-135826
    Inhibitor 98.39%
    Necroptosis-IN-1, an analog of Necrostatin-1, is a potent necroptosis inhibitor. Necroptosis-IN-1 is a RIPK inhibitor.
  • HY-148382
    RI-962 is a potent and selective receptor-interacting protein kinase 1 (RIPK1) inhibitor. RI-962 inhibits RIPK1 with an IC50 value of 35.0 nM. RI-962 can be used for the research of nervous system diseases and inflammatory diseases.
  • HY-149258
    Inhibitor 99.83%
    KWCN-41 is a selective and efficient inhibitor of RIPK1 kinase with an IC50 value of 88 nM. KWCN-41 specifically inhibits cell necrosis but does not inhibit apoptosis. KWCN-41 also has anti-inflammatory effects.
  • HY-151542
    MLKL-IN-4 (compound 56) is a potent MLKL (Mixed lineage kinase domain-like protein) inhibitor. MLKL-IN-4 inhibits necroptosis in HT-29 cells and acts downstream of MLKL phosphorylation, with EC50 of 82 nM. MLKL-IN-4 is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
  • HY-N10520
    Pectic acid
    Pectic acid (Methyl protopectin), a polygalacturonic acid, induces cell apoptosis and necrosis in pituitary tumor cells. Pectic acid can be used in the research of cancers and autoimmune disease.
  • HY-144277
    RIPK1-IN-12 is a potent RIPK1 inhibitor. RIPK1-IN-12 inhibits necroptosis in both human and mouse cells, with EC50 values of 1.6 and 2.9 nM, respectively.
  • HY-156119
    MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor targeting Mixed Lineage Kinase domain-like (MLKL). MLKL-IN-6 inhibits cell necrosis. MLKL-IN-6 inhibits MLKL phosphorylation and oligomerization during cell necrosis, inhibits immune cell death, and reduces the expression of adhesion factors. MLKL-IN-6 has low cytotoxicity, and it inhibits hepatic stellate cell activation, reduces liver fibrosis marker levels, and has anti-fibrotic effects.