MGCD265

MGCD265 is an orally bioavailable, small molecule tyrosine kinase inhibitor of Met, VEGFR1, VEGFR2, VEGFR3, Ron, and Tie2 with IC50 of 1 nM, 3 nM, 3 nM, 4 nM, 2 nM and 7 nM, respectively. Dysregulation of Met signaling has been implicated in the initiation, progression and metastasis of human cancers. Met is overexpressed in non-small-cell lung cancer and its lack of staining in normal lung tissue makes it an attractive target. Inhibition of these RTKs and their downstream signaling pathways may result in the inhibition of tumor angiogenesis and tumor cell proliferation in tumors overexpressing these RTKs. MGCD-265 has demonstrated a favorable safety profile and can be combined safely with other cancer therapeutics such as docetaxel and erlotinib. In preclinical studies, MGCD265 demonstrated nanomolar potency in enzyme and cellular assays and up to 100% of tumor growth inhibition in a broad range of xenograft models. Daily oral administration of MGCD265 was found to be well tolerated at doses of 24, 48 and 96 mg/m2.