TNF

Synonyms

Tumor Necrosis Factor (TNF Superfamily, Member 2), Tumor Necrosis Factor Ligand 1F, Tumor Necrosis Factor-Alpha, TNF Superfamily, Member 2, TNF, Macrophage-Derived, TNF, Monocyte-Derived, APC1 Protein, TNLG1F, DIF, ICD1, Tumor necrosis factor, NTF, TNF-a, TNF-alpha, ICD2, N-terminal fragment, TNF, Tumor necrosis factor ligand superfamily member 2, Cachectin, TNFSF2, TNFA

Description

Tumor necrosis factor α is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as T helper cells, natural killer cells, neutrophils, mast cells, eosinophils, and neurons.TNF is a member of the TNF superfamily, consisting of various transmembrane proteins with a homologous TNF domain.Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective . Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line . Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 .The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

KO Status

F2 (-/-)

Drug Information

Launched drugs: 46
Drugs in clinical trials: 63
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Luminol sodium

MP-1032

Approved

Selvim, Metrio

Immune System Diseases, Psoriasis

Etanercept biosimilar (Mochida)

LBEC-0101

Approved

Mochida Pharmaceutical Co Ltd

Arthritis, Rheumatoid, Arthritis, Juvenile

Infliximab

TA-650

Approved

Janssen Global Services Llc

Giant Cell Arteritis, Spondylitis, Ankylosing, Arthritis, Rheumatoid, Sarcoidosis, Pediatric Crohn's disease, Mucocutaneous Lymph Node Syndrome, Psoriasis, Pediatric ulcerative colitis, Colitis, Ulcerative, Arthritis, Psoriatic, Parapsoriasis, Uveitis, Pulmonary Disease, Chronic Obstructive, Crohn Disease, Behcet Syndrome

Etanercept biosimilar (AryoGen Biopharma)

Approved

Aryogen Biopharma

Spondylitis, Ankylosing, Arthritis, Rheumatoid, Arthritis, Juvenile, Psoriasis, Arthritis, Psoriatic

Etanercept biosimilar (Shanghai CP Guojian Pharmaceutical)

301S

Approved

Shanghai Cp Guojian Pharmaceutical Co Ltd, Cipla Gmbh

Arthritis, Rheumatoid, Spondylitis, Ankylosing, Psoriasis

Infliximab (dyyb)

CT-P13

Approved

Celltrion

Spondylitis, Ankylosing, Arthritis, Rheumatoid, Psoriasis, Arthritis, Psoriatic, Colitis, Ulcerative, Urologic Neoplasms, Crohn Disease

Etanercept biosimilar (Hanwha Chemical)

HD-203, MK-8953

Approved

Hanwha Chemical

Spondylitis, Ankylosing, Arthritis, Rheumatoid, Psoriasis, Arthritis, Psoriatic

Adalimumab biosimilar (Bio-Thera Solutions)

BAT-1406

Approved

Bio-Thera Solutions Ltd

Spondylitis, Ankylosing, Arthritis, Rheumatoid, Psoriasis, Uveitis, Crohn Disease

Infliximab biosimilar (Bionovis/The Instituto Vital Brazil)

Approved

Bionovis, The Instituto Vital Brazil

Arthritis, Rheumatoid, Spondylitis, Ankylosing, Psoriasis, Arthritis, Psoriatic, Colitis, Ulcerative, Crohn Disease

Adalimumab biosimilar (Innovent Biologics)

IBI-303

Approved

Innovent Biologics(Suzhou) Co Ltd

Arthritis, Rheumatoid, Spondylitis, Ankylosing, Psoriasis

References

Title

Authors

Source

Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome

Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A., Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N., Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A., Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A.,

Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986)

Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin

Pennica D., Nedwin G.E., Hayflick J.S., Seeburg P.H., Derynck R., Palladino M.A., Kohr W.J., Aggarwal B.B., Goeddel D.V.,

Nature 312:724-729(1984)

Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor

Shirai T., Yamaguchi H., Ito H., Todd C.W., Wallace R.B.,

Nature 313:803-806(1985)

Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization

Nedwin G.E., Naylor S.L., Sakaguchi A.Y., Smith D.H., Jarrett-Nedwin J., Pennica D., Goeddel D.V., Gray P.W.,

Nucleic Acids Res. 13:6361-6373(1985)

Molecular cloning of the complementary DNA for human tumor necrosis factor

Wang A.M., Creasey A.A., Ladner M.B., Lin L.S., Strickler J., van Arsdell J.N., Yamamoto R., Mark D.F.,

Science 228:149-154(1985)

Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor

Marmenout A., Fransen L., Tavernier J., van der Heyden J., Tizard R., Kawashima E., Shaw A., Johnson M.J., Semon D., Mueller R., Ruysschaert M.-R., van Vliet A., Fiers W.,

Eur. J. Biochem. 152:515-522(1985)

Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment

Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G., Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J., Cohen D.,

Nat. Genet. 3:137-145(1993)

A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC

Neville M.J., Campbell R.D.,

J. Immunol. 162:4745-4754(1999)

Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse

Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.,

Genome Res. 13:2621-2636(2003)

Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection

Kim Y.J., Lee H.-S., Yoon J.-H., Kim C.Y., Park M.H., Kim L.H., Park B.L., Shin H.D.,

Hum. Mol. Genet. 12:2541-2546(2003)

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