BMS-599626 is a pyrrolotriazine-based inhibitor of HER1, HER2, and HER4 kinases at IC50s of 20 nM, 30 nM, and 190 nM, respectively. Aside from micromolar potency for Lck and MEK (4 uM, and 2.5 uM, respectively), it is highly selective (>40 uM) over a wide panel of kinases. [1] Studies indicate that BMS-599626 inhibits HER1 and HER2 through distinct mechanisms. BMS-599626 is believed to be ATP competitive for HER1, while ATP-non-competitive for HER2. [1] Proliferation of cell lines dependent on HER1 and HER2 was measured in the range of 0.24 to 1 uM; cell lines not dependent on HER signaling were not affected by BMS-599626.

In Sal2 tumor cell lines, BMS-599626 was found to inhibit phosphorylation of CD8HER2 and MAPK in a dose-dependent manner. [1] In OV202 cells, BMS-599626 has been shown to work in synergy with IGF-1R inhibitors by the mechanism of enhanced apoptosis. [2]