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ApoptosisNecroptosis
Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The signaling pathway responsible for carrying out necroptosis is generally understood. TNFα leads to stimulation of its receptor TNFR1. TNFR1 binding protein TNFR-associated death protein TRADD and TNF receptor-associated factor 2 TRAF2 signals to RIPK1 which recruits RIPK3 forming the necrosome also named ripoptosome. Phosphorylation of MLKL by the ripoptosome drives oligomerization of MLKL, allowing MLKL to insert into and permeabilize plasma membranes and organelles. Integration of MLKL leads to the inflammatory phenotype and release of damage-associated molecular patterns (DAMPs), which elicit immune responses.
Necrostatin 2
T12203L852391-19-6
Necrostatin 2 is a necrotic protein and receptor-interacting protein kinase 1 (RIPK1) inhibitor used to study inner ear disorders such as sudden deafness, dizziness and tinnitus.
- $57
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Necroptosis-IN-3
T64349547698-18-0
Necroptosis-IN-3 (Cyclohexanecarboxamide, N-(2-thienylmethyl)-) (Compound 69) is a Necroptosis inhibitor that inhibits TNF-α induced necroptosis. Necroptosis-IN-3 (Compound STX1638) also inhibits 11β-HSD1.
- $35
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CDDO-3P-Im
T136031883650-95-0
CDDO-3P-Im is an orally active inhibitor of necroptosis with chemopreventive effects. CDDO-3P-Im can be used in studies about ischemia reperfusion.
- $96
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Necrostatin-5
T37558337349-54-9
Necrostatin-5 (Nec-5) is a selective RIP1 kinase inhibitor and cell necrosis inhibitor that prevents the death of Fadd-deficient Jurkat cells treated with TNF-α, with an EC50 of 240 nM.
- $38
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Cathepsin B
T800529047-22-7
Cathepsin B is a cysteine protease located within the subcellular endosomes and lysosomal compartments that mediates apoptosis and can be used in cancer research.
- $565
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Necrocide 1
T780511247028-61-0
Necrocide 1 is a potent inducer of cancer cell necrosis that is not inhibited by caspase blockers, anti-apoptotic BCL2 overexpression, or TNFα neutralization at nanomolar concentrations, and acts through the mitochondrial regulatory pathway.
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Cholicamideβ
T79707
Cholicamideβ (compound 6), a self-assembling small molecule cancer vaccine adjuvant, forms low cytotoxicity virus-like particles and upon binding to peptide antigens, enhances dendritic cell-mediated antigen presentation and induces antigen-specific T-cell responses, with the ability to induce apoptosis and necrosis [1].
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Anticancer agent 146
T79347
Anticancer Agent 146 (Compound 1.19) acts as a necroptosis inducer and demonstrates anti-tumor efficacy in the MDA-MB-231 mouse xenograft model [1].
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FGFR1/VEGFR2-IN-2
T89865
FGFR1 VEGFR2-IN-2 (compound 6) is a dual inhibitor targeting both VEGFR2 and FGFR1 with IC50 values of 0.025 µM and 0.026 µM, respectively. This compound also exhibits inhibitory effects on EGFR and PDGFR-β, with IC50 values of 0.106 µM and 0.077 µM, respectively. FGFR1 VEGFR2-IN-2 demonstrates significant anticancer activity in the NCI-60 cell lines, showing a growth inhibition (GI) of 60.38%. In T-47D cell lines, it achieves an IC50 of 8.51 µM, exhibits anti-migratory properties, induces cell cycle arrest in the G1 phase, and promotes both apoptosis and necrosis. Additionally, while it has an IC50 greater than 100 µM in MCF-7 cell lines, it does so with an IC50 of 69.17 µM in MDA-MB-231 cell lines and shows no toxicity to normal cells.
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EGFR-IN-134
T201573
EGFR-IN-134 (compound 3f) is a triazolo[3,4-a]quinoline derivative and functions as a potent EGFR inhibitor with an IC50 of 0.023 µM. It induces apoptosis and necrosis in cells, and causes cell cycle arrest in the G2 M and pre-G1 phases. EGFR-IN-134 modulates the expression of apoptosis-regulating proteins by downregulating anti-apoptotic protein Bcl2 and upregulating pro-apoptotic proteins p53, Bax, and caspases 3, 8, and 9, demonstrating significant antiproliferative and anticancer activities.
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RIP1 kinase inhibitor 8
T796052226735-54-0
RIP1 Kinase Inhibitor 8 (Compound 77), a potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitor, exhibits an IC50 of 20 nM and effectively prevents necrotic cell death. It also demonstrates a favorable pharmacokinetic profile across multiple species [1].
- $1,520
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TP4 (Nile tilapia piscidin)
T802861429184-62-2
TP4 (Nile tilapia piscidin) is an orally active, piscidin-like antimicrobial peptide that inhibits various gram-positive and gram-negative bacterial strains with a minimum inhibitory concentration (MIC) ranging from 0.03 to 10 μg mL. It demonstrates hemolytic activity and promotes immune response, antioxidant activity, and intestinal health in the presence of bacterial infections. Additionally, TP4 has an anti-tumor effect and induces necrosis in cancer cells by triggering mitochondrial dysfunction [1] [2] [3].
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MLKL-IN-6
T79731
MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein. It effectively prevents MLKL phosphorylation and oligomerization, which are critical steps in cell necrosis. Additionally, MLKL-IN-6 restrains immune cell death, diminishes adhesion factor expression, exhibits low cytotoxicity, impedes hepatic stellate cell activation, decreases liver fibrosis marker levels, and exerts anti-fibrotic effects [1].
- $1,320
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RIP3 activator 1
T2016771456899-52-7
RIP3 Activator 1 (compound C8) is an effective RIP3 activator that inhibits cell growth and induces necroptotic cell death (necroptosis) and autophagy through the RIP3 p62 Keap1 signaling pathway. Additionally, this compound enhances the expression of p-MLKL and promotes the accumulation of LC3-II and p62 proteins.
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