tumour necrosis factor shed form   Click here for help

GtoPdb Ligand ID: 5074

Abbreviated name: TNF shed form
Synonyms: cachectin | necrosin | TNF alpha soluble form | tumor necrosis factor soluble form
Immunopharmacology Ligand
Comment: TNFα is a pro-inflammatory, acute phase cytokine involved in systemic inflammation.
The TNF precursor is expressed as a membrane-bound ligand, which is cleaved by TACE/ADAM17 to form this shed (or 'soluble') bioactive cytokine containing just the extracellular domain, and that circulates predominantly as a homotrimer. Recombinant TNF is used as an immunostimulant under the INN tasonermin.

Circulating active TNF-α is the principal molecular target of the anti-TNF therapeutics infliximab and adalimumab. A smaller and longer acting and orally deliverable anti-TNF biologic called V565 is in early stage clinical development [2]. Considering alternative modes of administration, V565 is a heavy chain only variable domain anti-TNF nanobody generated in Ilama that is further modified to enhance resistance to protease-mediated degradation. It binds shed TNF-α with similar affinity to infliximab and adalimumab, and also inhibits biological responses mediated by membrane-bound TNF-α [2]. If this design strategy proves successful, V565 will be the first orally active anti-TNF therapy. V565 is being evaluated for potential to treat Crohn's disease (see Phase 2 study NCT02976129).
Species: Human
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Classification Click here for help
Compound class Endogenous peptide in human, mouse or rat
Ligand families/groups Tumor necrosis factor superfamily ligands
Synonyms Click here for help
cachectin | necrosin | TNF alpha soluble form | tumor necrosis factor soluble form
Gene/Precursor Click here for help
Gene symbol Gene name Species Precursor protein name Synonyms
TNF tumor necrosis factor Human prepro-tumor necrosis factor DIF, TNFA, TNF-alpha, TNFSF2, TNF superfamily, member 2, tumor necrosis factor (TNF superfamily, member 2)
Database Links Click here for help
DrugBank Target P01375 (Hs)
Ensembl Gene ENSG00000204490 (Hs)
GtoPdb PubChem SID 178101767
Human Protein Atlas ENSG00000204490 (Hs)
Immunopaedia Search tumour necrosis factor shed form
UniProtKB P01375 (Hs)
Wikipedia Tumor_necrosis_factor-alpha