Target Information
Target General Information | Top | |||||
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Target ID |
T16486
(Former ID: TTDI02380)
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Target Name |
TNFA messenger RNA (TNF mRNA)
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Synonyms |
Tumour necrosis factor alpha (mRNA); Tumour necrosis factor (mRNA); Tumor necrosis factor ligand superfamily member 2 (mRNA); Tumor necrosis factor (mRNA); TNFalpha (mRNA); TNFSF2 (mRNA); TNFA (mRNA); TNF-alpha (mRNA); TNF-a (mRNA); TNF alpha (mRNA); Cachectin (mRNA)
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Gene Name |
TNF
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Target Type |
Discontinued target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Crohn disease [ICD-11: DD70] | |||||
2 | Rheumatoid arthritis [ICD-11: FA20] | |||||
3 | Schizophrenia [ICD-11: 6A20] | |||||
Function |
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. Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
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BioChemical Class |
mRNA target
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UniProt ID | ||||||
Sequence |
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
1 | ISIS 104838 | Drug Info | Discontinued in Phase 2 | Rheumatoid arthritis | [2] | |
2 | PNU-282987 | Drug Info | Terminated | Schizophrenia | [3], [4] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
References | Top | |||||
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REF 1 | Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013426) | |||||
REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3988). | |||||
REF 4 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. | |||||
REF 5 | Antisense oligonucleotide blockade of tumor necrosis factor-alpha in two murine models of colitis. J Pharmacol Exp Ther. 2003 Jan;304(1):411-24. |
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