In vitro
BMS-599626(AC480) inhibited HER1 and HER2 with IC50 of 20 and 30 nM. BMS-599626(AC480) is highly selective against a broad panel of diverse protein kinases. BMS-599626 abrogated HER1 and HER2 signaling and inhibited the proliferation of tumor cell lines that are dependent on these receptors, with IC50 in the range of 0.24 to 1 micromol/L. In tumor cells that are capable of forming HER1/HER2 heterodimers, BMS-599626 inhibited heterodimerization and downstream signaling. BMS-599626(AC480) significantly enhanced the radiosensitivity of HN-5 cells. In HN-5 cells, BMS-599626(AC480) inhibit the expression of pEGFR, pHER2, cyclins D and E, pRb, pAkt, pMAPK, pCDK1 and 2, CDK 6, and Ku70 proteins. BMS-599626(AC480) also induced accumulation of cells in the G1 cell cycle phase, inhibited cell growth, enhanced radiosensitivity, and prolonged the presence of gamma-H2AX foci up to 24 h after radiation.But BMS-599626(AC480) did not increase the percentage of cells undergoing radiation-induced apoptosis.
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