Structure analysis reveals the flexibility of the ADAMTS-5 active site

A ((1S,2R)‐2‐hydroxy‐2,3‐dihydro‐1H‐inden‐1‐yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP‐2, MMP‐8, MMP‐9, and MMP‐13. Modeling studies had predicted that this compound would not bind to ADAMTS‐5 (a disintegrin and metalloproteinase with thrombospondin motifs‐5) due to its shallow S1′ pocket. However, inhibition analysis revealed it to be a...