ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family comprises 19 secreted zinc metalloendopeptidases that are vital regulators of the extracellular matrix (ECM) and vascular homeostasis. These enzymes possess a complex domain architecture consisting of a catalytic metalloproteinase domain and multiple C-terminal thrombospondin type 1 motifs that confer high substrate specificity and tissue localization. Key therapeutic targets within the family include ADAMTS4 and ADAMTS5 (aggrecanases), which drive the degradation of cartilage in osteoarthritis, and ADAMTS13, the protease responsible for cleaving large von Willebrand factor (VWF) multimers to prevent excessive blood clotting. Clinical strategies involve the use of small-molecule inhibitors and monoclonal antibodies to halt joint destruction in arthritis, as well as recombinant enzyme replacement therapies like TAK-755 for treating thrombotic thrombocytopenic purpura (TTP). A primary challenge in drug development for this class is achieving high selectivity to avoid the 'musculoskeletal syndrome' associated with the non-specific inhibition of other matrix metalloproteinases.

Other names

ADAMTS familyA disintegrin and metalloproteinase with thrombospondin motifsAggrecanasevon Willebrand factor-cleaving protease

Protease inhibition; Enzyme replacement therapy