CGP77675

CGP77675 is a potent inhibitor of Src family kinases. CGP77675 inhibits Src, EGFR, KDR, v-Abl, and Lck with IC50s of 0.02, 0.15, 1.0, 0.31, and 0.29 μM, respectively. Anticancer activity[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

IC50: 0.02 μM (Src), 0.15 μM (EGFR), 1.0 μM (KDR), 0.31 μM (v-Abl), 0.29 μM (Lck)[1]

CGP77675 inhibits phosphorylation of peptide substrates and autophosphorylation of purified Src (IC50s of 5-20 and 40 nM, respectively) [1]. CGP77675 dose dependently inhibits phosphorylation of poly-Glu-Tyr with an IC50 value of 5.5 nM, and of the optimal Src substrate (OSS) peptide with an IC50 value of 16.7 nM. These IC50 values are similar to the value obtained with chicken Src (20 nM)[1]. CGP77675 inhibits the parathyroid hormone-induced bone resorption in rat fetal long bone cultures with an IC50 of 0.8μM[1]. 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 (IC50 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 (1, 5, and 25 mg/kg; injected s.c.; twice a day) inhibits IL-1b-induced hypercalcemia in Mice[1]. 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[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-1b-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.

[1]. Missbach M, et al. A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellularsubstrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999 May;24(5):437-49.