PF-05212384

Phosphatidylinositol-3-kinases (PI3Ks) act in concert with mTOR complexes to regulate signaling pathways that have critical roles in cancer and other diseases.{15415,27164} PF-05212384 is a potent, dual PI3K/mTOR inhibitor (IC50 values are 0.4 and 5.4 nM for PI3K? and PI3K?, respectively, and 1.6 nM for mTOR).{29095,29096} It is active both in vitro and in vivo, inhibiting the growth of cancer cells in culture or in xenografts in mice when delivered intravenously.{29095,29096} PF-05212384 blocks the proliferation of liver cancer stem cells, and this effect is enhanced in combination therapy with the multikinase inhibitor BAY-43-9006 (Item No. 10009644).{29089} PF-05212384 action also enhances the effectiveness of cetuximab or radiation therapy in human head and neck cancer models.{29088,29094}