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A novel bone resorption inhibitor, A-75943, was isolated from Streptomyces sp. SANK 61296. Its structure was determined to be (1"S,2'R,3"S,4S',5"S)-2-[(3",5"- dimethyl-2"-oxocyclohexan-1"-yl)-6'-oxotetrahydropyran-4'-yl ]acetamide by spectral analyses and chemical conversion of cycloheximide. A-75943 inhibited bone resorption in vitro in a concentration-dependent manner with an IC50 of 0.35 microM, and also displayed an inhibitory effect on bone resorption in thyroid and parathyroid-extracted rats.

A Novel Bone Resorption Inhibitor, A-75943 Isolated from Streptomyces sp. SANK 61296.