Mubritinib

Mubritinib (TAK-165) is a novel HER2 selective tyrosine kinase inhibitor for the treatment of cancer. Mubritinib displays > 4000-fold selectivity over EGFR, FGFR, PDGFR, JAK1 and Src. Mubritinib displays no inhibitory activities against PC-3 cells with HER2 expressed very faintly with IC50 of 4.62 μM, as well as EGFR-overexpressing HT1376 and ACHN cell lines with IC50 of >25 μM. Mubritinib exhibits potent antiproliferative effects in ErbB2-overexpressing cancer cell lines (IC50 = 5 nM in BT474 breast cancer cells) and significantly inhibits bladder, breast and prostate cancer xenograft growth in vivo. Mubritinib (TAK-165) significantly inhibited growth of UMUC-3, ACHN, and LN-REC4 in the xenograft model. The antitumor effect (T/C [%]=growth of Mubritinib (TAK-165) treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively.