ADAM17

ADAM17 (A Disintegrin and Metalloproteinase 17), also known as TNF-α-converting enzyme (TACE), is a membrane-anchored metalloprotease critical for ectodomain shedding of transmembrane proteins. It cleaves substrates including TNF-α, EGFR ligands (e.g., TGF-α, amphiregulin), and adhesion molecules (e.g., L-selectin), thereby regulating inflammation, epithelial repair, and cell signaling. Key pathways influenced by ADAM17 include EGFR/MAPK, NF-κB, and TNF signaling. Dysregulation of ADAM17 is implicated in inflammatory diseases (e.g., rheumatoid arthritis, sepsis), cancer progression, and cardiovascular disorders. Therapeutic targeting of ADAM17 remains challenging due to its broad substrate spectrum and structural homology with other ADAMs. Selective inhibitors (e.g., DPC333, INCB7839) and monoclonal antibodies have shown efficacy in preclinical models, with some advancing to early-phase clinical trials for oncology and autoimmune indications.