XL518 ³

Stage

Phase 1

Status

A phase 1 trial of XL518 in patients with advanced solid tumors is ongoing.

Indications

Advanced Solid Tumors

Principal Targets

Cell proliferation: MEK

MEK is a component of the RAS/RAF/MEK/ERK kinase signaling pathway.
Genetic lesions that activate this pathway are common in human tumors, with activating mutations in K-RAS occurring in approximately 30 percent of tumors, and activating mutations in B-RAF occurring in approximately 60 percent of melanomas.

The RAS/RAF/MEK/ERK kinase signaling pathway integrates signals coming from outside cells to regulate cell growth and proliferation.

Preclinical Data

Preclinical data were presented most recently at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2007.

In vitro analyses indicate that XL518 is a potent and selective non-competitive inhibitor of MEK1, a component of the RAS/RAF/MEK/ERK signaling pathway. Dysregulation of this pathway contributes to many of the hallmarks of cancer cells: uncontrolled proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis.
Inhibition of MEK activity by XL518 prevents phosphorylation and activation of ERK, thus inhibiting downstream signaling activity. Administration of XL518 results in sustained inhibition of pERK in multiple preclinical tumor models. Notably, pERK inhibition in Colo-205 xenograft tumors is substantially more durable than other MEK inhibitors currently in clinical trials.
XL518 exhibits dose-dependent tumor growth inhibition and regression at well-tolerated doses in multiple preclinical human tumor xenograft models.

View the poster

Information on Clinical Trials

Information about ongoing clinical trials of Exelixis' investigational product candidates is available at ClinicalTrials.gov, a service of the U.S. National Institutes of Health. General information about clinical trials and issues related to participating in clinical trials also is available at ClinicalTrials.gov.

Related Publications

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

Footnotes:
3 In March 2008, Genentech exercised its option to further develop and commercialize XL518.