A disintegrin and metalloproteinase (ADAM) (ADAM)

The A disintegrin and metalloproteinase (ADAM) family consists of transmembrane and secreted proteins that play essential roles in the proteolytic release of cell-surface molecules, a process known as ectodomain shedding [1, 3]. These proteins are characterized by a modular structure that includes both a metalloproteinase domain responsible for catalytic activity and a disintegrin-like domain that facilitates cell adhesion and protein-protein interactions [2, 5]. Key members such as ADAM10 and ADAM17 (also known as TNF-alpha converting enzyme, or TACE) are critical regulators of signaling pathways, as they release the extracellular domains of receptors and ligands including TNF-alpha, EGFR ligands, and Notch [1, 4]. In disease, dysregulation of ADAM activity is linked to cancer progression, chronic inflammation, and neurodegenerative disorders such as Alzheimer's disease, where ADAM10 acts as the alpha-secretase [3, 4]. Therapeutic strategies typically focus on small molecule inhibitors or monoclonal antibodies designed to block the catalytic activity of specific ADAM members, though broad-spectrum inhibition has historically been limited by safety concerns like musculoskeletal toxicity [1, 18].

Other names

ADAM familyADAM proteinsAdamalysinsMDC familyMetalloproteinase-like, disintegrin-like, cysteine-rich proteinsA disintegrin and metalloproteinase domain-containing proteinSheddasesADAMTS family

Small molecule inhibitors typically target the catalytic zinc-dependent metalloproteinase domain to block the ectodomain shedding of cell-surface proteins, thereby modulating the availability of active ligands and the activation of signaling receptors.