BMS 599626 dihydrochloride is a potent and selective inhibitor of EGFR and ErbB2 with IC50 values of 22 and 32 nM, respectively [1].
The epidermal growth factor receptor (EGFR) is the cell-surface receptor for epidermal growth factor and plays an important role in tumor invasion and cancer cell proliferation. Receptor tyrosine-protein kinase erbB-2 (ErbB2) is a human epidermal growth factor receptor and plays a critical role in breast cancer.
BMS 599626 dihydrochloride is a potent and selective EGFR and ErbB2 inhibitor. BMS-599626 inhibited HER4 with IC50 value of 190 nM. In Sal2, N87 and GEO tumor cells, BMS-599626 inhibited phosphorylation of HER1 and HER2 in a dose-dependent way and inhibited cell proliferation. In AU565 breast cancer cells, BMS-599626 (1μM) inhibited HER1/HER2 heterodimer formation [1]. In tumor cells that forming HER1/HER2 heterodimers, BMS-599626 inhibited heterodimerization [2].
In the L2987 human lung tumors xenograft models, BMS-599626 (60 mg/kg) inhibited and delayed tumor growth in a dose-dependent way [1].
References:
[1]. Gavai AV, Fink BE, Fairfax DJ, et al. Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases. J Med Chem, 2009, 52(21): 6527-6530.
[2]. Wong TW, Lee FY, Yu C, et al. Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin Cancer Res, 2006, 12(20 Pt 1): 6186-6193.