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The Galapagos-Servier selective ADAMTS-5 metalloproteinase inhibitor (GLPG1972) recently completed a Ph. II study for knee osteoarthritis. Identification of small molecule clinical candidates for metalloproteinases is challenging due to selectivity issues and the chemical properties of needed metal-binding groups. The hydantoin is proposed to act as a bidentate zinc-binding motif (see this paper for an X-ray co-crystal structure of a hydantoin inhibitor coordinated to zinc). The mechanism of action targeting cartilage is interesting but the compound did not meet its primary or secondary endpoints in its recent Ph. II trial.