Drug Detail

Information about XL765

Generic Name
Brand Name (US)
Drug Type
Approval Status
Phase 2
Overall Strategy
Oncogenic Signal Path Based
Block related tumor signal paths
Drug Category
mTOR inhibitor PI3K inhibitor

Preclinical Data

XL765 targets both PI3K and mTOR, key kinases in the PI3K signaling pathway. mTOR is a serine/threonine kinase that controls the protein translation machinery and hence cell proliferation. mTOR is activated by growth factors via PI3K and AKT, but is also activated in a PI3K-independent fashion in response to nutrient and energy levels. Hence, in some tumors, targeting both PI3K and mTOR may provide additional benefit compared with selectively targeting PI3K. XL765 is a potent inhibitor of PI3K and mTOR, and has shown attractive pharmacokinetic and pharmacodynamic properties and compelling anti-tumor activity in several preclinical xenograft models, both as a single agent and in combination with chemotherapy.

Preclinical data presented at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2007 demonstrate that XL765 inhibits PI3K pathway signaling in cellular assays and in xenograft tumor models. In addition, administration of XL765 results in the inhibition of tumor growth and angiogenesis, and of tumor cell survival in xenograft models. XL765 is orally available, exhibits durable activity in pharmacodynamic studies, and is well tolerated at doses that exhibit anti-tumor activity. XL765 also enhances the apoptotic activity of chemotherapeutic agents (paclitaxel or carboplatin) in xenograft tumor models.