Mubritinib

Mubritinib (TAK-165) is a potent and selective EGFR2/HER2 inhibitor with an IC₅₀ of 6 nM. IC50 & Target: IC50: 6 nM (EGFR2)^[1] In Vitro: Mubritinib (TAK-165) specifically inhibits HER2 tyrosine kinase with an IC₅₀ 6 nM and does not inhibit other types tyrosine kinase up to 25 000 nM. Mubritinib inhibits HER2 phosphorylation and its down-stream Akt and MAPK in HER2 strongly expressing cells (BT474 breast cancer cell line). Mubritinib sensitivity depends on HER2 levels of each cell line. Especially, BT474 cells which over-express HER2 strongly is highly sensitive (IC₅₀=0.005 µM) and PC-3 cells which express HER2 very weakly is less sensitive (IC₅₀=4.62 µM). But, HT1376 and ACHN cells that over-expressed EGFR showed high IC₅₀ (IC₅₀>25 µM)^[1]. In Vivo: In the xenograft model, treatment with Mubritinib (TAK-165) significantly inhibits growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect after 14 days treatment are 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively^[1].