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Necroptosis

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.

  • 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 the death of immune cells, diminishes the expression of adhesion factors, and exhibits low cytotoxicity. Furthermore, it impedes the activation of hepatic stellate cells, decreases levels of liver fibrosis markers, and exerts anti-fibrotic effects [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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  • 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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  • 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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  • 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.
    • $41
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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 exhibits inhibition of various gram-positive and 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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  • Necrostatin-5
    T37558337349-54-9
    Necrostatin-5 (Nec-5) is a selective inhibitor of RIP1 kinase and a cell necrosis inhibitor that prevents the death of Fadd-deficient Jurkat cells treated with TNF-α with an EC50 value of 240 nM.
    • $38
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