Biological Activity
Lapatinib ditosylate monohydrate (GW572016 ditosylate monohydrate) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1].
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[1]. 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[1]. Lapatinib (GW2016; 1-10 µM; 72 hours; HN5 cells) treatment results in induces G1 arrest[1]. Western Blot Analysis[1] Cell Line: BT474 and HN5 cells Concentration: 0.03 µM, 0.1 µM, 0.3 µM, 1 µM, 3 µM, or 10 µM Incubation Time: 6 hours Result: Inhibited receptor autophosphorylation of EGFR and ErbB-2 in a dose-responsive manner. Phosphorylation of serine 473 of AKT was also inhibited in a dose-dependent manner. Cell Proliferation Assay[1] Cell Line: HN5, A-43, BT474, N87, and CaLu-3 cells Concentration: Incubation Time: 72 hours Result: Inhibited the growth of tumor cells overexpressing EGFR or ErbB-2. Cell Cycle Analysis[1] Cell Line: HN5 cells Concentration: 1 µM, or 10 µM Incubation Time: 72 hours Result: Resulted in induction of 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[1]. Animal Model: CD-1 nude female mice (4-6 weeks old) with HN5 cells[1] Dosage: 30 mg/kg, 100 mg/kg Administration: Oral administration; twice daily; for 21 days Result: Inhibited tumor xenograft growth of the HN5 cells in a dose-responsive manner.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.