X-379 Selective c-Met Inhibitor

Mesenchymal-epithelial transition factor (c-Met), also known as hepatocyte growth factor receptor (HGFR), is a tyrosine kinase receptor that plays an imperative role in angiogenesis and tumor growth.  Similar to its role in normal tissue, c-Met deregulation enhances tumor cell proliferation, survival, motility and invasion leading to metastasis.  The mechanism of inappropriate signaling is through mutation, overexpression, ligand binding or interaction with other cell surface receptors.

The c-met receptor or its ligand HGF is deregulated in a wide variety of human tumors: including gastric, renal, breast, colon, hepatocellular, lung, glioblastoma, sarcoma, and head and neck tumors. Overexpression occurs in all stages of the malignant process indicating this pathway as a promising drug target in a range of cancers.  In addition, amplification of c-met has been shown to cause resistance to treatment with EGFR family inhibitors.

Xcovery’s X-379 is an oral, potent and selective inhibitor of c-Met autophosphorylation.  X-379 is potent against most c-Met mutations and is able to completely inhibitor c-Met at tolerable doses.  It is expected that X-379 will be broadly active in human tumors, particularly in combination with other tyrosine kinase inhibitors for which resistance develops as a function of c-met activation.