Molecular Target
Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Cellline Data Matrix
Gene Expression
Gene Copy Number Variation
RNA Interference
Mutations

Molecular Target Synopsis - TNF (P01375) - Overview

Protein


TNF, Tumor necrosis factor
UniProt P01375

Also Known as TNFA_HUMAN, TNF, TNFA, TNFSF2

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., The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. Homotrimer. Interacts with SPPL2B.

Drugs


TNF is targeted by Approved Drugs Etanercept, Mirostipen, Infliximab, Adalimumab, Certolizumab Pegol. (see details)

Sub-cellular localization


UniProt: TNF is active in the following subcellular-locations: Cell membrane, Membrane, Secreted.



UniProt
GO terms

Mutations in Cancer


Please click the link to see mutations reported in Cancer Gene Census

Please click the link to see mutations reported in ICGC

According to the Cosmic, TNF has 4 reported mutations in cell lines ....p.P215P (1), p.P215L (1), p.R207* (1), p.P146L (1)

The mutation data was obtained from the Sanger Institute Catalogue Of Somatic Mutations In Cancer web site, http://www.sanger.ac.uk/cosmic
Bamford et al (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer, 91,355-358.
Please click the link to see mutations reported in MoKCa

(see details)

Gene Copy Number Variation


TNF has an absolute copy number > 7 in 1 cell lines, the highest copy numbers are in cell lines : SUDHL1. (see details)

Gene Expression


In the NCI - NCI 60 Reference panel, the highest expressing cell lines are: HCT116, OVCAR8. (see details)

RNA Interference


TNF was reported in the following RNAI studies:

AACR Journals - Results of primary druggable genome v2 (DG2) Achilles heel siRNA screen in KMS11 multiple myeloma cells, the highest RNAi cell lines are: KMS11. (see details)

3D Structures


There are 12 structures (45 chains) solved for TNF
1 are solved in complex with at least one small molecule ligand


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TNF has been screened with 188 compounds (272 bioactivities), 16 compounds have bioactivities that show binding affinity of <= 500nM (17 bioactivities). (see details)