The human epidermal growth factor receptor 2 (HER2) is overexpressed in nearly 15-30% of breast cancers, and is associated with aggressive metastasis resulting in poor patient survival. Current treatment options including the monoclonal antibody targeted therapy, trastuzumab (Herceptin®), usually results in acquired resistance within a year. The dual EGFR/HER2 kinase inhibitor lapatinib (Tykerb/Tyverb®) showed promising phase II results, but a recent phase III trial found no significant advantage to single-agent lapatinib treatments over trastuzumab treatments alone. Recently our group developed four novel naphthoquinones highly effective at auto- phosphorylation inhibition of the HER2 Y1248 residue in breast tumor cells, as well as growth inhibition of trastuzumab resistant oncogenic isoform HER2Δ16 cells. In the initial high-throughput assay, all four compounds showed significant growth inhibition of the MCF7-HER2, MCF7-HER2Δ16 breast cancer cell lines.<br/>

Synthesis and biological evaluation of naphthoquinones as HER2 kinase inhibitors

251st National Meeting (2016)

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