CGP77675 (ZINC1488120) is a potent and selective inhibitor of Src family kinase with IC50s of 5-20 and 40 nM for the phosphorylation of peptide substrates and autophosphorylation of purified Src. CGP77675 exhibits anticancer activity.

EGFR:0.15 μM (IC50), Src:0.02 μM (IC50), Lck:0.29 μM (IC50), v-ABL:0.31 μM (IC50), KDR:1.0 μM (IC50)

CGP77675 inhibits Src, EGFR, KDR, v-Abl, and Lck with IC50s of 20, 150, 1000, 310, and 290 nM, respectively. CGP77675 dose-dependently inhibits phosphorylation of poly-Glu-Tyr (IC50 = 5.5 nM), and of the optimal Src substrate (OSS) peptide (IC50 = 16.7 nM). In rat fetal long bone cultures, CGP77675 inhibits the parathyroid hormone-induced bone resorption (IC50 = 0.8 μM). In Src-overexpressing IC8.1 cells, CGP77675 (0.04-10 μM) dose-dependently inhibits phosphorylation of Fak (IC50 = 0.2 μM) and paxillin(IC50 = 0.5 μM), but not of Src(IC50 = 5.7μM)[3].

In female rats of the Sprague-Dawley-derived strain Tif:RAlf, CGP77675 (10 and 50 mg/kg;orally) partially prevents bone loss and rescues bone microarchitectural features. In male mice, CGP77675 (1, 5, and 25 mg/kg; s.c.) inhibits IL-1β-induced hypercalcemia without affecting serum amyloid protein levels[3].