Lapatinib (4-Methylbenzenesulfonate)

Lapatinib (GW572016) tosylate is a potent, orally active 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].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> Apoptosis >> Ferroptosis

Signaling Pathways >> Autophagy >> Autophagy

EGFR:10.2 nM (IC50)

ErbB2:9.8 nM (IC50)

Lapatinib (GW2016; 0.03-10 µM; 6 hours; BT474 and HN5 cells) tosylate 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) tosylate 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]. Cell Proliferation Assay[1] Cell Line: HN5, A-43, BT474, N87, and CaLu-3 cells Concentration: 1 nM-100 µM 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. 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.

Lapatinib (GW2016; 30-100 mg/kg; oral administration; twice daily; for 21 days; CD-1 nude female mice) tosylate 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.

[1]. Rusnak DW, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94