CGP77675

CGP77675 is an orally active and potent inhibitor of Src family kinases. CGP77675 inhibits phosphorylation of peptide substrates and autophosphorylation of purified Src (IC₅₀s of 5-20 and 40 nM, respectively), and also inhibits Src, EGFR, KDR, v-Abl, and Lck with IC₅₀s of 5-20, 40, 20, 150, 1000, 310, and 290 nM, respectively. Anticancer activity^[1]. IC50 & Target: IC50: 0.02 μM (Src), 0.15 μM (EGFR), 1.0 μM (KDR), 0.31 μM (v-Abl), 0.29 μM (Lck)^[1] In Vitro: 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 0.8 μM^[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]. In Vivo: CGP77675 (1, 5, and 25 mg/kg; injected s.c.; twice a day) inhibits IL-1β-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].