CP-654577

CP-654577 is a selective ErbB2 inhibitor with an IC₅₀ of 11 nM. CP-654577 downregulates the Notch1 signaling pathway. CP-654577 upregulates p27^kip1, reduces the levels of Cyclins D and E, and inhibits G1 phase progression of the cell cycle. CP-654577 induces cell Apoptosis, downregulates activated Akt, and suppresses tumor growth in athymic mice. CP-654577 can be used in breast cancer-related research^[1][2][3]. In Vitro:CP-654577 (300-1000 nM) reduces Notch1 signaling (measured via CBF reporter activity) in ErbB2-overexpressing SKBR3 breast cancer cells, with 1000 nM causing a 50% reduction in activity^[1].
CP-654577 (300-1000 nM; 36 hours post-transfection) does not affect Notch1 (CBF reporter) or Wnt (TOP-luc) signaling in low-ErbB2-expressing MCF-7 breast cancer cells at concentrations of 300 nM and 1000 nM^[1].
CP-654577 (6 min) is a selective inhibitor of purified human erbB2 kinase, with 60-fold higher potency against erbB2 (IC₅₀ = 11 nM) than EGFr (IC₅₀ = 670 nM), and shows limited activity against other non-erbB family tyrosine kinases^[2].
CP-654577 (0.1-3 μM; 2 h pre-incubation before 15 min EGF stimulation) selectively inhibits erbB2 kinase activity in intact NIH 3T3 cells, potently suppressing EGF-induced phosphotyrosine levels in erbB2/EGFR chimera-transfected cells (to <5% of control at ≥0.3 μM) while only weakly inhibiting EGFR-transfected cells at equivalent concentrations^[2].
CP-654577 (24 h) potently inhibits the proliferation of SKBr3 human breast cancer cells with an IC₅₀ of 55 nM after 24 h of exposure^[2].
CP-654577 (50 nM-1000 nM; 2 h, 8 h, 12 h, 24 h) induces a concentration-dependent G₁ cell-cycle arrest in SKBr3 human breast cancer cells, with marked effects observed at 250 nM and 1000 nM after 8 h, 12 h, and 24 h of exposure^[2]. In Vivo:CP-654577 (25-100 mg/kg; i.p.; single dose) dose-dependently inhibits erbB2 tyrosine phosphorylation in FRE-erbB2 tumor xenografts, with an ED₅₀ of 43 mg/kg^[2].
CP-654577 (12.5-50 mg/kg; i.p.; twice daily; 7 days) dose-dependently inhibits the growth of FRE-erbB2 tumor xenografts, achieving 65% growth inhibition at 50 mg/kg twice daily after 7 days of treatment^[2].