tcsc0831 Lapatinib (ditosylate)

Lapatinib ditosylate is a potent EGFR and ErbB2 inhibitor with IC₅₀ of 10.2 and 9.8 nM, respectively.



IC50 & Target: IC50: 10.2 nM (EGFR), 9.8 nM (ErbB2)^[1]

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].