CGP77675 hydrate is an orally active and potent inhibitor of Src family kinases. CGP77675 hydrate inhibits phosphorylation of peptide substrates and autophosphorylation of purified Src ( IC 50 s of 5-20 and 40 nM, respectively),and also inhibits Src, EGFR, KDR, v-Abl, and Lck with IC 50 s of 0.02, 0.15, 1.0, 0.31, and 0.29 μM, respectively. CGP77675 hydrate can be useful for the treatment of diseases associated with elevated bone loss and has anticancer activity[1].

CGP77675 hydrate inhibits phosphorylation of poly-Glu-Tyr in a dose-dependent manner with an IC 50 value of 5.5 nM, and of the optimal Src substrate (OSS) peptide with an IC 50 value of 16.7 nM. These IC 50 values are similar to the value obtained with chicken Src (20 nM) [1]. CGP77675 hydrate inhibits the parathyroid hormone-induced bone resorption in rat fetal long bone cultures with an IC 50 of 0.8 μM [1]. CGP77675 hydrate (0.04-10 μM; 2 hours) potently inhibits tyrosine phosphorylation of the Src substrates Fak and paxillin, but has much less effect on Src (IC 50 values 0.2, 0.5, and 5.7μM) in IC8.1 cells [1]. Cell Viability Assay [1] Cell Line: MC3T3-E1 cells Concentration: 0.2, 1, and 5 μM Incubation Time: 3 days Result: Did not influence cell viability for up to 3 days of treatment. Western Blot Analysis [1] Cell Line: Src-overexpressing IC8.1 cells Concentration: 0.04, 0.2, 1, 5, and 10 μM Incubation Time: 2 hours Result: Dose dependently inhibited phosphorylation of Fak and paxillin, but not of Src.

CGP77675 hydrate (1, 5, and 25 mg/kg; injected s.c.; twice a day) inhibits hypercalcemia induced by IL-1β in Mice [1]. CGP77675 hydrate (10 and 50 mg/kg; administered orally; twice a day for 6 weeks) partially prevents bone loss and rescues bone microarchitectural features in young ovx rats [1]. Animal Model: Male mice (Tif:MAGf; Novartis Animal Farm) of 25-30 g body [1] Dosage: 1, 5, and 25 mg/kg Administration: Injected s.c.; twice a day Result: Prevented IL-1β-induced hypercalcemia in mice without affecting serum amyloid protein levels. Animal Model: Eight-week-old (175-209 g) female rats of the Sprague-Dawley-derived strain Tif:RAlf [1] Dosage: 10 and 50 mg/kg Administration: Administered orally; twice a day for 6 weeks Result: Partly prevented bone loss.