In preclinical studies, XL147 slowed tumor growth or caused tumor shrinkage in multiple preclinical cancer models, including breast, lung, ovarian, and prostate cancers, and gliomas. XL147 has also been shown to enhance the anti- tumor effects of several chemotherapeutic agents and an inhibitor of epidermal growth factor receptor (EGFR) in preclinical cancer models.
Mechanism of action
XL147 is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Activation of PI3K is a frequent event in human tumors, promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in...