MedKoo product information:

XL765

Description of XL-765: XL-765 is a PI3K/mTOR dual kinase inhibitor XL765 is an orally bioavailable small molecule targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinases in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR dual kinase inhibitor XL765 inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cell populations. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion in response to nutrient and energy deprivation. Accordingly, this agent maybe more potent compared to an agent that inhibits either PI3K kinase or mTOR kinase alone. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    Exelixis and  sanofi-aventis.

Exelixis is developing XL765 in collaboration with sanofi-aventis. Based on clinical data available to date, Exelixis and sanofi are pursuing a broad clinical development program for XL765, evaluating the compound as a single agent and in multiple combination regimens in a variety of cancer indications. Ongoing clinical trials include phase 1b/2 trials in combination with temozolomide in patients with glioblastoma, and in combination with erlotinib in patients with non-small cell lung cancer, and a phase 1 trial in patients with solid tumors or lymphoma. [source: http://www.exelixis.com/pipeline/xl765].

Clinical trial results on XL-765:  June 7, 2010 7:35 AM EDT; Exelixis, Inc. (Nasdaq: EXEL) today reported updated interim data from three ongoing trials of XL765 (SAR245409), an orally available small molecule inhibitor of phosphoinositide-3-kinase (PI3K) and mTOR. Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation, survival, and resistance to chemotherapy and radiotherapy. The pathway also has been implicated as a mediator of resistance to agents targeting epidermal growth factor receptor (EGFR) family members. The presentations will be made at the 2010 Annual Meeting of the American Society of Clinical Oncology, which is being held June 4-8 in Chicago. Exelixis is developing XL765 with sanofi-aventis.

“XL765 has unique clinical potential because it inhibits the signaling of both PI3K and mTOR, two important nodes in this critical pathway,” said Michael M. Morrissey, Ph.D., president of research and development at Exelixis. “PI3K signaling is dysregulated in a broad spectrum of human cancers, and mTOR is a well validated target for cancer therapy. The results from these studies suggest that this novel compound may have clinical activity as a single agent and in combination with targeted agents and chemotherapy. These data support the ongoing broad phase 1/2 clinical program and further phase 2 evaluation that sanofi-aventis and Exelixis have planned for XL765.” [source: http://www.streetinsider.com/Corporate+News/Exelixis+%28EXEL%29+Updates+on+XL765+Trials+of+PI3K+and+mTOR/5705385.html].