ADAM metallopeptidase domain 17 (ADAM17)

ADAM metallopeptidase domain 17 (ADAM17), commonly known as TNF-alpha converting enzyme (TACE), is a membrane-bound disintegrin metalloproteinase responsible for the proteolytic cleavage (shedding) of various cell surface proteins. Its most prominent role is the conversion of membrane-anchored pro-tumor necrosis factor-alpha (pro-TNF-alpha) into its active soluble form, a key driver of systemic inflammation. Beyond TNF-alpha, ADAM17 processes a wide array of substrates including growth factors like TGF-alpha, cytokine receptors, and adhesion molecules, making it a central regulator of immune responses and cellular signaling. Due to its critical role in inflammatory pathways, ADAM17 is a major therapeutic target for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease, as well as certain cancers where it promotes growth factor signaling. However, developing selective inhibitors remains a challenge due to the enzyme's broad substrate profile and the potential for adverse effects from inhibiting its diverse physiological functions.

Other names

TNF-alpha converting enzymeTACECD156bCSVPTNF-alpha convertaseDisintegrin and metalloproteinase domain-containing protein 17

Inhibition of the catalytic metalloproteinase domain to prevent the proteolytic cleavage and release of soluble TNF-alpha and other membrane-bound substrates.