Biological Activity
Lapatinib (GW572016) is a potent EGFR and ErbB2 inhibitor with IC50s of 10.2 and 9.8 nM, respectively.
In Vitro
The IC50 of Lapatinib (GW2016) values for inhibition of enzyme activity are generated by measuring inhibition of phosphorylation of a peptide substrate. With the exception of ErbB-4 (IC50, 367 nM), Lapatinib is >300-fold selective for EGFR and ErbB-2 over other kinases tested[1]. IC50 values of Lapatinib (GW2016) for BT474, SKBR3, EFM192A, HCC1954, MDAMB453 and MDAMB231 cells is 36±15.1 nM, 80±17.3 nM, 193±66.5 nM, 416.6±180 nM, 6.08±0.825 μM and 7.46±0.102 μM, respectively. Treatment with Lapatinib results in IC50 values of ≤ 0.16 μM on the EGFR- and the ErbB-2-overexpressing tumor cell lines[2].
In Vivo
Lapatinib (GW2016) is potent at inhibiting the growth of BT474 and HN5 human tumor xenografts. A dose-responsive inhibition of both models occurred on treatment of tumor-bearing mice with 30 and 100 mg/kg Lapatinib orally, twice daily. Complete inhibition of tumor growth is seen at the 100 mg/kg dose. At this dose, there is <10% weight loss in treated animals over the course of the 21-day treatment. Lapatinib treatment inhibits tumor xenograft growth of the HN5 and BT474 cells in a dose-responsive manner at 30 and 100 mg/kg orally, twice daily, with complete inhibition of tumor growth at the higher dose[1]. Lapatinib (100 mg/kg/day, oral gavage) induces severe oxidative damage in the cardiac tissue of rat[3].
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.