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):

By Effects:	Inhibitors (64) Control (1) Activators (4) Inducers (83)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-176219

Bcl-2-IN-23	Inducer
Bcl-2-IN-23 (compound 5) is a selective inhibitor targeting Bcl-2. The IC₅₀ of Bcl-2-IN-23 in HTB-140, HeLa and SW620 cells is 25.7-33.7 μM. Bcl-2-IN-23 can non-covalently competitively bind to Bcl-2 protein, significantly reduce its expression, and induce late apoptosis and necroptosis of cancer cells. Bcl-2-IN-23 enhances the sensitivity of cancer cells to apoptosis and reduces the release of IL-6 inflammatory factors by disrupting the Bcl-2-mediated mitochondrial apoptosis inhibition pathway. Bcl-2-IN-23 can be used for anti-apoptosis research of malignant tumors such as melanoma, cervical cancer, and colorectal cancer.

HY-153435

RIP1 kinase inhibitor 5	Inhibitor	98.49%
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	Activator
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-179112

PROTAC IKKβ/NR4A1 degrader-1	Inducer
PROTAC IKKβ/NR4A1 degrader-1 is a highly efficient and effective dual-PROTAC degrader targeting IKKβ and NR4A1. PROTAC IKKβ/NR4A1 degrader-1 can increase the levels of caspase 3 and cleaved caspase 3 proteins, while the necroptosis marker RIP kinase remained unchanged, indicating that it can induce apoptosis. PROTAC IKKβ/NR4A1 degrader-1 can be used for the study of Acute myeloid leukemia (AML). Red: IKKβ/NR4A1 ligand (HY-13067); Blue: E3 ligase CRBN ligand (HY-14658); Black: Linker (HY-79577).

HY-181073

Apoptosis/necroptosis inducer 1	Inducer
Apoptosis/necroptosis inducer 1 is an orally active and brain-penetrant apoptosis and necroptosis inducer. Apoptosis/necroptosis inducer 1 induces mitochondria-dependent (intrinsic pathway) apoptosis. Apoptosis/necroptosis inducer 1 induces necroptosis by activating the TNF-α/NF-κB/MAPK signaling pathway. Apoptosis/necroptosis inducer 1 exhibits antiproliferative activity in glioblastoma cell lines and multiple solid tumor types. Apoptosis/necroptosis inducer 1 inhibits growth of orthotopic glioblastoma in animal models and improves survival rate. Apoptosis/necroptosis inducer 1 can be used for the research of glioblastoma.

HY-162097

RIPK1-IN-20	Inhibitor
RIPK1-IN-20 (compound 13c) has a favorable RIPK1 kinase inhibition activity with an IC₅₀ value of 59.8 nM. RIPK1-IN-20 blocks TNFα-induced necroptosis in both human and murine cells (EC₅₀=1.06–4.58 nM).

HY-178163

Zharp1-163	Inhibitor
Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (K_D = 240 nM; IC₅₀ = 406.1 nM). Zharp1-163 inhibits the cellular activation of RIPK1, RIPK3 and MLKL in response to necroptotic stimulation. Zharp1-163 markedly attenuates TNF-α (HY-P1875)-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Zharp1-163 significantly alleviates acute kidney injury associated with both necroptosis and ferroptosis in models induced by Cisplatin (HY-17394) and ischemia-reperfusion. Zharp1-163 can be used for the study of diseases associated with cell death pathways, such as kidney disease.

HY-172909

RIPK3-IN-5	Inhibitor
RIPK3-IN-5 (compound 32) is a potent RIPK3 inhibitor with an IC₅₀ of 27 nM. RIPK3-IN-5 also inhibits necroptosis with an EC₅₀ of 0.45 μM.

HY-178464

RIPK1-IN-34	Inhibitor
RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC₅₀ = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC₅₀ ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).

HY-179386

PARP1/EZH2-IN-1	Inducer
PARP1/EZH2-IN-1 is a selective PARP1 and EZH2 dual inhibitor. PARP1/EZH2-IN-1 has IC₅₀s of 28 nM, 414 nM and 74 nM for PARP1, PARP2 and EZH2, respectively. PARP1/EZH2-IN-1 inhibits the proliferation and migration of TNBC cells (triple-negative breast Cancer cells). PARP1/EZH2-IN-1 induces PANoptosis (Apoptosis, Pyroptosis and Necroptosis), increases the level of reactive oxygen species (ROS), and activates related inflammatory pathways. PARP1/EZH2-IN-1 can be used in triple-negative breast cancer research.

HY-183564

RIPK1/RIPK3-PPI-IN-1	Inhibitor
RIPK1/RIPK3-PPI-IN-1 is an orally active dual-target inhibitor of RIPK1/RIPK3, with a K_d value of 2.4 nM for RIPK1 and 24 nM for RIPK3. RIPK1/RIPK3-PPI-IN-1 inhibits the phosphorylation of RIPK1, RIPK3 and MLKL, thereby suppressing necroptosis. RIPK1/RIPK3-PPI-IN-1 restores body temperature, improves survival rate, and reduces IL-1β/IL-6 levels in serum and multiple organs of Mus musculus, thus alleviating TNF-α-induced systemic inflammatory response syndrome. RIPK1/RIPK3-PPI-IN-1 can be used in research related to systemic inflammatory response syndrome.

HY-175030

TNI-97	Inducer
TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC₅₀ of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.

HY-B1984S

p,p'-DDD-d₈	Inducer
p,p'-DDD-d₈ is the deuterium labeled p,p'-DDD[1]. 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.

HY-179680

RIPK1-IN-38	Inhibitor
RIPK1-IN-38 is an orally active RIPK1 inhibitor with an IC₅₀ value of 27 nM. RIPK1-IN-38 can inhibit the phosphorylation of RIPK1 and its downstream signaling molecules RIPK3 and MLKL. RIPK1-IN-38 exhibits anti-necroptotic activity. RIPK1-IN-38 has excellent anti-inflammatory efficacy in both the SIRS model and GVHD model. RIPK1-IN-38 can be used for the research of inflammatory and immune-related diseases.

HY-B0863S5

Glyphosate-¹³C,¹⁵N-1
Glyphosate-¹³C,¹⁵N-1 is the ¹³C- and ¹⁵N-labeled Glyphosate (HY-B0863). 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-184001

LT-1339-553	Inhibitor
LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC₅₀ values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.

HY-144277

RIPK1-IN-12	Inhibitor
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-W162436

MCC1019	Inducer
MCC1019 is a selective PLK1 PBD inhibitor with an IC₅₀ of 16.4 μmol/L. MCC1019 inactivates the AKT signaling pathway in cancer cells, and induces Apoptosis, Necroptosis and Autophagy. MCC1019 exhibits anticancer activity against lung cancer and prostate cancer.

HY-179037

NecroX-2	Inhibitor
NecroX-2 is a potent inhibitor of caspase-independent necrosis. NecroX-2 exhibits antioxidant activity by scavenging DPPH radicals and peroxynitrite. NecroX-2 inhibits t-BHP-induced mitochondrial ROS/RNS generation, and protects t-BHP and Doxorubicin (HY-15142A)-induced cell death in vitro. NecroX-2 can be used for research on neurological diseases.

HY-160170

Necrosis inhibitor 3	Inhibitor
Necrosis inhibitor 3 (compound B3) is a poteng inhibitor of necrosis, with the IC₅₀ value of 0.29 nM in HT29 cells.

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