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Tumor necrosis factor alpha (TNF-α) inhibitors reduce the production or signaling of a central inflammatory cytokine. In 1975 an endotoxin-induced serum factor that causes necrosis of tumors was described and named tumor necrosis factor. Cloning of human TNF in 1984 revealed a precursor related to lymphotoxin. Through its two receptors, TNF-α activates nuclear factor kappa B (NF-κB) and cell death pathways. Etanercept is a soluble receptor fusion protein that binds the cytokine, and C 87 is a small-molecule TNF-α inhibitor. In 1991 thalidomide was shown to inhibit TNF-α production by stimulated human monocytes, and its analogs lenalidomide and pomalidomide are also listed. Pathway compounds include the NF-κB inhibitor QNZ and necrostatin-1, an inhibitor of receptor-interacting protein kinase 1 (RIPK1).
Synonyms: Linomide; FCF89; ABR212616
Roquinimex (Linomide; PNU212616; ABR212616) is a quinoline derivative immunostimulant which increases NK cell activity and macrophage cytotoxicity; inhibits angiogenesis and reduces the secretion of TNF alpha.
Synonyms: γ-glutamylcysteine (TFA)
Gamma-glutamylcysteine (TFA) ((γ-glutamylcysteine (TFA)), an intermediate in glutathione (GSH) synthesis, is a dipeptide served as an essential cofactor for the antioxidant enzyme glutathione peroxidase (GPx).
(Rac)-Benpyrine, a racemate of Benpyrine, is a potent and orally active TNF-α inhibitor. (Rac)-Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research.
Synonyms: MTU
Methylthiouracil is an antithyroid agent. Methylthiouracil suppresses the production TNF-α and IL-6, and the activation of NF-κB and ERK1/2.
UCB-9260, an orally active compound, inhibits TNF signaling by stabilising an asymmetric form of the trimer. UCB-9260 is selective for TNF over other superfamily members, and binds TNF with a similar Kd of 13 nM.
Synonyms: Pedalitin permethyl ether
Sinensetin is a methylated flavone found in certain citrus fruits. pocess potent antiangiogenesis and anti-inflammatory, sinensetin enhances adipogenesis and lipolysis.
Synonyms: REN 1654; REN 1189
CPI-1189 (REN 1654, REN 1189) is the proapoptotic cytokine tumor necrosis factor (TNF) alpha inhibitor.
AR420626 is a selective agonist of free fatty acid receptor 3 (FFAR3, also known as GPR41), with an IC₅₀ of 117 nM. It demonstrates anti-inflammatory, antitumor, and antidiabetic activities. AR420626 improves neurogenic diarrhea by modulating neural pathways mediated by nicotinic acetylcholine receptors (nAChRs). In cancer models, it suppresses the growth of HepG2 xenografts and inhibits hepatoma cell proliferation through apoptosis induction. Additionally, AR420626 mitigates allergic asthma and eczema and enhances glucose uptake by activating FFAR3-mediated Ca²⁺ signaling, offering potential therapeutic benefits in metabolic disorders such as diabetes.
HS-276 is an orally bioavailable, potent, and highly selective inhibitor of transforming growth factor-β–activated kinase 1 (TAK1), with a Kᵢ of 2.5 nM. It exhibits strong inhibition of TAK1 and moderate activity against a panel of other kinases, including CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with respective IC₅₀ values ranging from 8.25 to 5585 nM. HS-276 is a valuable tool for investigating TAK1-mediated signaling pathways and holds therapeutic potential for inflammatory conditions such as rheumatoid arthritis (RA).
Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue that exhibits potent anti-inflammatory activity. It exerts its effects by blocking mitogen-activated protein kinase (MAPK) signaling and inhibiting the nuclear translocation of the NF-κB subunit p65, thereby suppressing key inflammatory pathways. Additionally, compound 5a27 reduces neutrophil infiltration and the production of pro-inflammatory cytokines. In vivo, it significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI), highlighting its potential as a therapeutic candidate for inflammatory and respiratory disorders.
Necroptosis-IN-1 is a potent inhibitor of necroptosis, primarily targeting receptor-interacting protein kinase (RIPK). This compound effectively hinders necroptotic cell death pathways, making it a valuable tool for research involving cell death mechanisms. Its application spans studies related to inflammation, neurodegeneration, and cancer, providing insights into the role of necroptosis in various pathological conditions.
TNF-α-IN-19 is a selective inhibitor of TNFα, effectively disrupting the interaction between TNFα receptor 1 (TNFαRI), TNF receptor-associated death domain (TRADD), and receptor-interacting protein 1 (RIP1). It exhibits EC50 values of 2.451 μM for TNFα, 3.792 μM for IL-1β, and 1.54 μM for the TNFα/IL-1β combination. Notably, TNF-α-IN-19 specifically inhibits the degradation of IκBα induced by TNFα stimulation, while showing no effect in IL-1β stimulated conditions. This compound is valuable for research into inflammatory pathways and therapeutic interventions in TNFα-mediated diseases.
Necrostatin-21 is a potent necroptosis inhibitor targeting receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase 3 (JNK3) with an EC50 of 0.5 μM. This compound demonstrates an ability to modulate cell death pathways, making it valuable for research into various conditions including infections, cardiovascular diseases, and neurodegenerative disorders such as Alzheimer’s disease. Its dual action on key kinases provides insight into the mechanisms underlying necroptosis and potential therapeutic approaches.
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VDX-111 is a necroptosis inducer that functions as an analog of vitamin D. It exerts cytotoxic effects in ovarian cancer cells by upregulating the RIPK1/RIPK3 pathway, leading to necroptotic cell death. Additionally, VDX-111 promotes cytokine expression and demonstrates significant antitumor activity in murine models, making it a valuable tool for cancer research focused on necroptosis.
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IDT is a TNFα modulator that targets and regulates the innate immune response. It has demonstrated significant efficacy in reducing paired helical filament tau and fibrillar amyloid accumulation, as well as enhancing the infiltration of neutrophils while decreasing TNFα expression within this population. IDT is a valuable reagent for research focused on Alzheimer’s disease and the underlying mechanisms of neuroinflammation.
CC-1069 is a TNF-α inhibitor that targets tumor necrosis factor-alpha, a key cytokine involved in inflammation and tumorigenesis. This compound has shown potential in inhibiting processes related to endothelial cell function. CC-1069 is particularly useful for investigating angiogenesis-dependent tumors, including gliomas, providing valuable insights into tumor growth and vascularization mechanisms in experimental research settings.
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TNF-α-IN-22 is a TNFα inhibitor that interferes with the downregulation of IkBα, leading to apoptosis and cell cycle arrest. This compound exhibits significant biological activity in studies related to inflammation and is particularly relevant in the investigation of triple-negative breast cancer. Its mechanism of action makes it a valuable tool for elucidating TNFα's role in cancer progression and therapeutic resistance.
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TNF-α-IN-9 is a targeted inhibitor of Tumor Necrosis Factor-alpha (TNF-α). This compound demonstrates low inhibitory activity, making it suitable for studies focused on the modulation of TNF-α signaling pathways. Researchers can use TNF-α-IN-9 to explore its potential effects in inflammatory diseases and related biological systems.
LMP-420 is a selective inhibitor of tumor necrosis factor-alpha (TNF-α). It effectively reduces the release of pro-inflammatory cytokines such as IL-1β and IL-2, while promoting the expression of the anti-inflammatory cytokine IL-10, and the anti-apoptotic proteins SOCS-1 and Mn-SOD. Additionally, LMP-420 downregulates chemokines like IP-10 and MCP-1, which diminishes immune cell infiltration. This reagent is valuable for studying conditions such as type 1 diabetes mellitus, inflammatory diseases including colitis, and co-infections involving HIV and Mycobacterium tuberculosis.
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Synonyms: H-TL1
Hydrostatin-TL1 is a nine-amino-acid peptide that serves as a TNF-α antagonist. By competitively inhibiting the interaction between TNF-α and its receptor TNFR1, Hydrostatin-TL1 reduces TNF-α-mediated cytotoxicity and inflammation. This peptide is valuable for research into TNF-α-associated inflammatory diseases, including rheumatoid arthritis, osteoporosis, and inflammatory bowel disease (IBD).
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D-Trimannuronic acid, a TNF receptor activator derived from alginate oligomers in seaweed, stimulates the secretion of TNF-α in mouse macrophage cell lines. This compound is valuable in research focused on inflammatory responses, pain mechanisms, and vascular dementia. Its unique biological activity provides insights into immune modulation and related therapeutic areas.
TNF-α-IN-27 is a selective TNF-α inhibitor, exhibiting a 64% inhibition rate at a concentration of 10 μM. This compound is valuable for research in inflammation and immunology, making it particularly relevant for studies related to conditions such as asthma. Its targeted action on TNF-α contributes to understanding the molecular mechanisms underlying inflammatory responses.
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Epaldeudomide is a potent TNF-α inhibitor, demonstrating over 50% inhibition at a concentration of 100 nM. This compound effectively inhibits the proliferation of various cancer cell lines, including MM.1S with an IC50 of less than 300 nM, as well as WSU-DLCL-2 and Rec-1, both exhibiting IC50 values below 100 nM. Epaldeudomide is recognized for its antineoplastic properties, making it a valuable tool for cancer research and therapeutic studies.
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TNF-α-IN-24 is a potent tumor necrosis factor-alpha (TNF-α) inhibitor with an IC50 of 4.1 nM. This compound is valuable for investigating the mechanisms underlying inflammatory and autoimmune disorders, particularly in models of rheumatoid arthritis and Crohn’s disease. Its specificity for TNF-α allows for targeted research in cytokine modulation and potential therapeutic development.
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Synonyms: (-)-Shegansu B; (R)-Parvifolol D
Cis-Shegansu B is a selective TNF-α inhibitor, derived from the plant Gnetum cleistostachyum. It demonstrates modest inhibitory activity, achieving a 5% reduction in TNF-α levels at a concentration of 10 μM. This compound can be utilized in research focusing on inflammatory pathways and may provide insights into therapeutic approaches for TNF-α related diseases.
