AS2690168 is a novel orally available, selective RANKL signal transduction inhibitor, reduces TRAP staining of sRANKL-stimulated RAW264 cells with IC50 of 0.28 uM, suppresses RANKL-induced osteoclastogenesis.AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells with 37.1% and 98.9% inhibiyion at 0.3 and 3.0 uM, respectively.AS2690168 also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC50 value of 0.46 uM.AS2690168 (3 mg/kg, p.o.) completely suppressed the decrease in femoral bone mineral content in an sRANKL-induced osteopenic mice model, also significantly suppressed the decrease in femoral bone mineral density and increase in serum tartrate-resistant acid phosphatase-5b levels in ovariectomized rats at doses of 0.3, 1 and 3 mg/kg.AS260168 suppressed the increase in urine deoxypyridinoline in a rat prednisolone-induced osteoporosis model at 10 mg/kg.

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