2. Signaling Pathways
  3. Apoptosis
  4. Necroptosis

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 (165):

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-W144308
    Tetrachlorohydroquinone
    		Inducer 98.45%
    Tetrachlorohydroquinone (TCHQ) is a metabolite of Pentachlorophenol. Tetrachlorohydroquinone induces reactive oxidant stress (ROS), inhibits apoptosis and induces necrosis in primary mouse splenocytes. Tetrachlorohydroquinone increases DNA lesions and induces oxidative stress in rodents.
    Tetrachlorohydroquinone
  • HY-163740
    VEGFR-2-IN-46
    		Inducer
    VEGFR-2-IN-46 (compound 4d) is a potent VEGFR-2 inhibitor with an EC50 value of 67.0 nM. VEGFR-2-IN-46 shows cytotoxicity and induces cell cycle arrest at the G2/M phase. VEGFR-2-IN-46 induces necrosis and apoptosis.
    VEGFR-2-IN-46
  • HY-155146
    Anticancer agent 146
    		Inducer
    Anticancer agent 146 (compound 1.19) is a necroptosis inducer. Anticancer agent 146 has anti-tumor efficacy in the mouse MDA-MB-231 xenograft model.
    Anticancer agent 146
  • HY-162348
    Antitumor agent-145
    		Inhibitor
    Antitumor agent-145 (Compound Ir5) is a tumor inhibitor with remarkable fluorescence and mitochondrial targeting, which exerts anti-cancer effects by inducing necroptosis and activating the necroptosis-related immune response.
    Antitumor agent-145
  • HY-147521
    Antitumor photosensitizer-3
    Antitumor photosensitizer-3 (Compound I) is a chlorin derivative. Antitumor photosensitizer-3 induces tumor cells apoptosis and necrosis under 650 nm laser irradiation. Antitumor photosensitizer-3 exhibits lower skin photo-toxicity than positive reference m-THPC in vivo.
    Antitumor photosensitizer-3
  • HY-149080
    Antiparasitic agent-16
    		Inducer
    Antiparasitic agent-16, a pyridine-thiazolidinone, has anti-Trypanosoma cruzi and leishmanicidal activities. Antiparasitic agent-16 has IC50s of 1.0 μM and 0.6 μM against trypomastigote and amastigote forms of T. cruzi. Antiparasitic agent-16 has IC50s of 150.2 μM and 16.75 μM against trypomastigote and amastigote forms of L. amazonensis. Antiparasitic agent-16 induces parasite cell death through necrosis induction. Antiparasitic agent-16 induces morphological changes such as shortening, retraction and curvature of the parasite body and leakage of internal content with T. cruzi trypomastigotes.
    Antiparasitic agent-16
  • HY-161911
    Necroptosis-IN-5
    		Inhibitor
    Necroptosis-IN-5 (Compound 26) is an orally active necroptosis inhibitor. Necroptosis-IN-5 also exhibits potent inhibitory activity against receptor-interacting protein kinase 1 (RIPK1). Necroptosis-IN-5 can be used to study necroptosis-related inflammatory diseases, neurodegenerative diseases, and cancers.
    Necroptosis-IN-5
  • HY-178380
    HDAC8-IN-14
    		Activator
    HDAC8-IN-14, a curcuminoid derivative, is a selective HDAC8 inhibitor with a Ki of 9 nM. HDAC8-IN-14 induces the production of reactive oxygen species (ROS), disrupts mitochondrial membrane potential, and promotes apoptosis. HDAC8-IN-14 can significantly promote the accumulation of cells in the sub-G0/G1 phase, consistent with apoptotic or necrotic cell death. HDAC8-IN-14 induces upregulation of cytochrome c, cleaved caspase-3, and the pro-apoptotic protein Bak while leaving the anti-apoptotic Bcl-2 levels unaltered. HDAC8-IN-14 can be used for the study of leukemia.
    HDAC8-IN-14
  • HY-178762S
    RIPK1-IN-35
    		Inhibitor
    RIPK1-IN-35 is a selective and orally active RIPK1 inhibitor with an IC50 of 5.33 nM. RIPK1-IN-35 has a potent protective effect against necroptosis in both human and murine cells. RIPK1-IN-35 shows good therapeutic effects in both TNF-α-induced systemic inflammatory response syndrome and DSS (HY-116282C)-induced inflammatory bowel disease models. RIPK1-IN-35 can be used to the study of inflammatory diseases related to necroptosis.
    RIPK1-IN-35
  • HY-162569
    Ru-TRZ2
    		Inducer
    Ru-TRZ2 is a potent ruthenium-based chemotherapeutic agent. Ru-TRZ2 induces apoptosis and necroptosis. Ru-TRZ2 shows antitumor activity.
    Ru-TRZ2
  • HY-151542
    MLKL-IN-4
    		Inhibitor
    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, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    MLKL-IN-4
  • HY-100573R
    Necrosulfonamide (Standard)
    		Inhibitor
    Necrosulfonamide (Standard) is the analytical standard of Necrosulfonamide (HY-100573). This product is intended for research and analytical applications. 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.
    Necrosulfonamide (Standard)
  • HY-N8380
    (-)-Latifolin
    		Inducer
    (-)-Latifolin, a flavonoid, induces apoptotic cell death by targeting PI3K/AKT/mTOR/p70S6K signaling. (-)-Latifolin significantly inhibits the cell proliferation of oral squamous cell carcinoma (OSCC), and causes the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of FAK/Src. (-)-Latifolin suppresses autophagic-related proteins and autophagosome formation. (-)-Latifolin inhibits necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). (-)-Latifolin has beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities.
    (-)-Latifolin
  • HY-Y0698R
    Thioacetamide (Standard)
    Thioacetamide (Standard) is the analytical standard of Thioacetamide (HY-Y0698). This product is intended for research and analytical applications. 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.
    Thioacetamide (Standard)
  • HY-130369
    NSC10010 hydrochloride
    		Inducer
    NSC10010 hydrochloride inhibits gammaherpesvirus associated B-lymphomas growth through activation of NF-kB and c-Myc-mediated signaling pathways. NSC10010 hydrochloride induces necrotic cell death in gammaherpesvirus infected B-cells. NSC10010 hydrochloride is also an inhibitor of Mtb ClpC1 ATPase.
    NSC10010 hydrochloride
  • HY-B1145R
    Chlorhexidine dihydrochloride (Standard)
    		Inducer
    Chlorhexidine dihydrochloride (Standard) is the analytical standard of Chlorhexidine dihydrochloride (HY-B1145). This product is intended for research and analytical applications. Chlorhexidine dihydrochloride is a orally active cationic antimicrobial agent that targets microbial cell membranes. Chlorhexidine dihydrochloride binds to cell membrane phospholipids non-specifically, destroys membrane structure and induces leakage of cell contents. Chlorhexidine dihydrochloride has broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria. Chlorhexidine dihydrochloride can interfere with membrane permeability, cause protein precipitation and energy metabolism disorders, such as rapid inhibition of microbial growth and induction of cell death (necrosis or apoptosis).
    Chlorhexidine dihydrochloride (Standard)
  • HY-121261
    Antineoplastic agent-1
    		Inducer
    Antineoplastic agent-1 is an alkylating agent and a genotoxic agent that can induce DNA damage. Antineoplastic agent-1 can lead to irreversible damage and progressive death of liver cells due to necroptosis and apoptosis. Antineoplastic agent-1 can cause alkylation damage to hematopoietic cells and stromal cells in the bone marrow. Antineoplastic agent-1 can be used in tumor research.
    Antineoplastic agent-1
  • HY-B1984R
    p,p'-DDD (Standard)
    		Inducer
    p,p'-DDD (Standard) is the analytical standard of p,p'-DDD (HY-B1984) . This product is intended for research and analytical applications. p,p'-DDD (4,4’-DDD) is an organochlorine insecticide, a major metabolite of p,p'-DDT. p,p'-DDD is an agonist at estrogen receptor α(ERα) and ERβ. p,p'-DDD increases DNA damage, apoptosis and necrosis in peripheral blood. p,p'-DDD stimulates cell proliferation in SKBR3 cells. p,p'-DDD activates the AP-1 transcription factor. p,p'-DDD decreases sleep times of barbiturates and steroids in rats.
    p,p'-DDD (Standard)
  • HY-108351R
    IM-54 (Standard)
    IM-54 (Standard) is the analytical standard of IM-54 (HY-108351). This product is intended for research and analytical applications. 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.
    IM-54 (Standard)
  • HY-N2414R
    Periplogenin (Standard)
    		Inducer
    Periplogenin (Standard) is the analytical standard of Periplogenin (HY-N2414). 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.
    Periplogenin (Standard)