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Two cartilage aggrecanases have been identified aggrecanase-1 ADAM-TS4 and aggrecanase-2 ADAM-TS5 and both enzymes have been shown very efficiently to cleave soluble aggrecan at the Glu373 Ala374 site. Matrix metalloproteinases MMP act primarily on the former bond and all MMPs found to be present in cartilage including MMP-1 MMP-2 MMP-3 MMP-7 MMP-8 MMP-9 MMP-13 and MT1-MMP are capable of cleaving aggrecan at this site in vitro4 7. In contrast SE206 is a nanomolar inhibitor of both MMPs and...

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