Lapatinib

A reversible, selective dual tyrosine kinase inhibitor of both EGFR and ErbB2 with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively; displays no significant activity against other kinases, including ErbB4, c-Src, and c-Raf1; reduces tyrosine phosphorylation of EGFR and erbB2, and inhibits activation of Erk1/2 and AKT both in vitro and in vivo; inhibits tumor xenograft growth of the HN5 and BT474 cells in a dose-responsive manner at 30 and 100 mg/kg; orally active.Breast Cancer Approved (In Vitro) :Lapatinib (GW2016; 0.03-10 μM; 6 hours; BT474 and HN5 cells) treatment inhibits receptor autophosphorylation of EGFR and ErbB-2 in a dose-responsive manner. Phosphorylation of serine 473 of AKT was inhibited by GW2016 in a dose-dependent manner.Lapatinib (GW2016; 72 hours; HN5, A-43, BT474, N87, and CaLu-3 cells) treatment has a selective inhibition of the proliferation of human tumor cell lines.Lapatinib (GW2016; 1-10 μM; 72 hours; HN5 cells) treatment results in induces G1 arrest. (In Vivo) :Lapatinib (GW2016; 30-100 mg/kg; oral administration; twice daily; for 21 days; CD-1 nude female mice) treatment inhibits tumor xenograft growth of the HN5 cells in a dose-responsive manner at 30 and 100 mg/kg, with complete inhibition of tumor growth at the higher dose.