necroptosis

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.

Necroptosis-IN-1 is a potent necroptosis inhibitor of RIPK1. It is an analog of Necrostatin-1.

Necroptosis-IN-5 (Compound 26) is an orally active inhibitor of necroptotic cell death (necroptosis). This compound also exhibits potent inhibitory activity against receptor-interacting protein kinase 1 (RIPK1). It can be utilized in research related to inflammatory diseases, neurodegenerative disorders, and cancer associated with necroptosis.

Necroptosis-IN-4 is an effective inhibitor of necroptosis, specifically targeting RIP kinase 1 (RIPK1) without inhibitory activity against RIPK3. It exhibits weak inhibitory effects on VEGFR1 2 and PDGFR-α.

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].

TopoisomeraseI II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.

Anticanceragent 267 (Compound 5q) serves as an activator of RIPK3 and MLKL. It effectively inhibits the proliferation of several cancer cell lines, with IC50 values of 9.79, 10.77, and 5.94 μM for MDA-MB-231, MDA-MB-486, and MCF-7, respectively. The compound induces cell cycle arrest at the subG1 phase and triggers necroptosis in MDA-MB-231 cells. Additionally, Anticanceragent 267 demonstrates antitumor activity in mouse xenograft models.

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].

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.

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].

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].

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].

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.

CDDO-3P-Im is an orally active inhibitor of necroptosis with chemopreventive effects. CDDO-3P-Im can be used in studies about ischemia reperfusion.

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.

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.

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.

Cathepsin B is a cysteine protease located within the subcellular endosomes and lysosomal compartments that mediates apoptosis and can be used in cancer research.

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.

(E)-Necrosulfonamide ((E)-Necrosulfonamide) is an inhibitor of necroptosis. Blocks mixed lineage kinase domain-like protein (MLKL), a critical substrate of receptor-interacting serine-threonine kinase 3 (RIP3) during necrosis. Prevents MLKL-RIP1-RIP3 necrosome complex from interacting with downstream necrosis effectors. Binds and inhibits gasdermin D. Inhibits pyroptosis.

Necrostatin 2 racemate (Necrostatin-2 racemate) is an potent and specific inhibitor of RIPK1.

Necrostatin-1 (Nec-1) (inactive control), an inactive analog of Necrostatin-1, functions as a potent inhibitor of necroptosis [1].

Compound Ir5 (Antitumor agent-145) serves as a tumor inhibitor characterized by significant fluorescence and mitochondrial targeting. It promotes anti-cancer activity by inducing necroptosis and stimulating the necroptosis-related immune response [1].

Kuguaglycoside C induces caspase-independent cell death, and is involved, at least in part, in the mechanism underlying cell necroptosis.