XL418  ¹

Stage

Phase I

Status

A Phase I trial of XL418 in patients with advanced solid tumors is ongoing.

Studies

Advanced Solid Tumors

Principal Targets

Cell growth and survival: AKT and S6 kinase (S6K)

• AKT and S6K act downstream of phosphoinositide-3-kinase (PI3K).
• AKT and S6K act upstream and downstream, respectively, of mammalian target of rapamycin (mTOR).
• Activation of these kinases is a frequent event in human tumors, promoting cell growth, survival, and resistance to chemotherapy and radiotherapy.

Preclinical Data

XL418 targets AKT and S6K, which are kinases downstream of PI3K. Their activation is a frequent event in human tumors and promotes cell growth, survival and resistance to chemotherapy and radiotherapy. Regulation of the pathway is complex, and inhibition at a single point can result in upregulation in the activity of other pathway components. AKT inhibitors that effectively inactivate the pathway are expected to reduce proliferation and to induce apoptosis (programmed cell death) in tumor cells and sensitize them to a wide range of chemotherapy. XL418 is a potent inhibitor that simultaneously targets the kinases AKT and S6K, with good oral bioavailability and efficacy in tumor xenograft models.

Related Publications

For publication information related to this compound, please see the Related Publications page.

Footnotes:
1 Pursuant to a product development and commercialization agreement between Exelixis and GlaxoSmithKline, GlaxoSmithKline has the option, after completion of proof-of-concept by Exelixis, to elect to develop up to three compounds in the Exelixis pipeline including XL880, XL820, XL184, XL844, XL999, XL281, XL418 and XL228.