BMS-599626

BMS-599626 is an orally bioavailable, small molecule pan-HER tyrosine kinase inhibitor developed for the treatment of cancers characterized by overexpression of human epidermal growth factor receptors (HER). It selectively inhibits HER1 (EGFR), HER2, and to a lesser extent HER4, with IC50 values of approximately 20 nM for HER1 and 30 nM for HER2. The drug acts as an ATP-competitive inhibitor for HER1 and an ATP-noncompetitive inhibitor for HER2, blocking receptor autophosphorylation, downstream signaling pathways (such as RAS/RAF/MEK/ERK and PI3K/AKT), cell proliferation, and tumor growth in preclinical models. BMS-599626 also inhibits the formation of active receptor heterodimers (e.g., between EGFR/HER2) that drive tumor progression. Additionally, it has been shown to inhibit the ABCG2 transporter function at non-cytotoxic concentrations, potentially reversing multidrug resistance in cancer cells. Developed by Bristol Myers Squibb, clinical development was discontinued in July 2015 after reaching phase I trials in advanced solid tumors[1][3][4][5][6].

Other names

714971-09-2