A disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) (ADAM17)

A disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), also known as TNF-alpha converting enzyme (TACE), is a membrane-bound enzyme that plays a pivotal role in the shedding of cell-surface proteins. Its primary biological function involves the proteolytic cleavage of membrane-bound pro-TNF-alpha into its active, soluble form, making it a central regulator of inflammatory responses (UniProt: P78536). Beyond TNF-alpha, ADAM17 processes a wide array of substrates, including EGFR ligands and various cytokine receptors, thereby influencing cell proliferation and signaling pathways (PubMed: 15121867). In pathological states such as rheumatoid arthritis and certain cancers, ADAM17 is often overexpressed or hyperactive, contributing to chronic inflammation and tumor progression (PubMed: 28243046). Therapeutic agents like the monoclonal antibody ASP5094 were developed to selectively inhibit ADAM17 activity to treat autoimmune conditions (PubMed: 26911374). Clinical studies have demonstrated that while ASP5094 effectively inhibits the target, it does not exhibit direct molecular or pharmacokinetic interactions with co-administered drugs like methotrexate (PubMed: 26911374). However, targeting ADAM17 remains challenging due to its broad substrate profile, which can lead to off-target effects and safety concerns in clinical settings.

Other names

TACETNF-alpha converting enzymeCD156bSnake venom-like proteaseMetalloproteinase 17

Monoclonal antibody-mediated inhibition of ADAM17 proteolytic activity, preventing the release of soluble TNF-alpha and other pro-inflammatory mediators from the cell surface.