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ADAM inhibitors block the a disintegrin and metalloproteinase (ADAM) sheddases ADAM10 and ADAM17. These zinc-dependent enzymes cut membrane proteins close to the cell surface and release their ectodomains. ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), releases soluble tumor necrosis factor-α (TNF-α) from its membrane-bound precursor. It also sheds ligands of the epidermal growth factor receptor (EGFR) and several cytokine receptors. ADAM10 cleaves Notch receptors after ligand binding, a step that Notch signaling requires during development. GI 254023X is listed as an ADAM10 inhibitor, and KP-457 as an ADAM17 inhibitor. Hydroxamate compounds such as TAPI-2 and TMI-1 inhibit TACE together with related matrix metalloproteinases, which are listed under MMP.
