BMS-599626 is a highly selective pan-HERKinase inhibitor with IC50 of 20 and 30 nM for the inhibition of HER1and HER2, respectively.
It is a highly selective and potent inhibitor of HER1 and HER2 kinases and inhibits tumor cell proliferation through modulation of receptor signaling. BMS-599626 inhibits HER1/HER2 receptor heterodimerization and provides an additional mechanism of inhibiting tumors in which receptor coexpression and heterodimerization play a major role in driving tumor growth.
ac480 (bms-599626) is a potent, selective inhibitor of human epidermal growth factor receptor (her) that inhibits her1 and her2 with ic values of 20 nm and 30 nm, respectively. ac480 has been proved to inhibit her1 in an atp-competitive manner. on the contrary, ac480 has shown to be an atp noncompetitive inhibitor of her2 [1]ac480 inhibited the proliferation of sal2 cells derived from a transgenic mouse tumor, breast tumor and gastric carcinoma cell lines, geo colon tumor cells, non–small-cell lung tumor cells line via her1 and/or her2 signalings [1].ac480 by oral administration has been demonstrated to suppress the growth of sal2 tumor, geo xenograft tumor, kpl-4 and bt474 breast tumors, n87 gastric tumor, a549 and l2987 non–small-cell lung tumors in nude mice [1].
[1] wong tw1, lee fy, yu c, luo fr, oppenheimer s, zhang h, smykla ra, mastalerz h, fink be, hunt jt,gavai av, vite gd. preclinical antitumor activity of bms-599626, a pan-her kinase inhibitor that inhibits her1/her2 homodimer and heterodimer signaling. clin cancer res. 2006 oct 15;12(20 pt 1):6186-93.
