Abbreviated name: TNF shed form
Synonyms: cachectin | necrosin | TNF alpha soluble form | tumor necrosis factor soluble form
Compound class:
Endogenous peptide in human, mouse or rat
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 [3]. 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 [3]. 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
View more information in the IUPHAR Pharmacology Education Project: tumour necrosis factor alpha |
Classification | |
Compound class | Endogenous peptide in human, mouse or rat |
Ligand families/groups | Tumor necrosis factor superfamily ligands |
Synonyms |
cachectin | necrosin | TNF alpha soluble form | tumor necrosis factor soluble form |
Gene/Precursor | ||||||||||
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Database Links | |
CATH/Gene3D | 2.60.120.40 |
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 |