CGP77675 is an orally active and potent inhibitor of Src family kinases. CGP77675 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 5-20, 40, 20, 150, 1000, 310, and 290 nM, respectively. Anticancer activity
In Vitro
CGP77675 dose dependently inhibits phosphorylation of poly-Glu-Tyr 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). CGP77675 inhibits the parathyroid hormone-induced bone resorption in rat fetal long bone cultures with an IC 50 of 0.8 μM. CGP77675 (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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell 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 AnalysisCell 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.
In Vivo
CGP77675 (1, 5, and 25 mg/kg; injected s.c.; twice a day) inhibits IL-1β-induced hypercalcemia in Mice . CGP77675 (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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male mice (Tif:MAGf; Novartis Animal Farm) of 25-30 g body 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 Dosage: 10 and 50 mg/kg Administration: Administered orally; twice a day for 6 weeks Result: Partly prevented bone loss.
Form:Solid
IC50& Target:IC50: 0.02 μM (Src), 0.15 μM (EGFR), 1.0 μM (KDR), 0.31 μM (v-Abl), 0.29 μM (Lck)
