MK-2461 is a potent inhibitor of Met, Flt1, Flt 3, Ron, PDGFRβ, and Mer with IC50 of 2.5 nM, 10 nM, 22 nM, 7 nM, and 24 nM, respectively.
c-Met, also named as hepatocyte growth factor receptor (HGFR) is a receptor tyrosine kinase that is essential for embryonic development and would healing. In many tumor cells, this molecular is overexpressed or mutated and was found to play important roles in tumor cell proliferation, survival, invasion, metastasis and angiogenesis.
In vitro, MK-2461treatment blocked hepatocyte growth factor/c-Met- dependent mitogenesis, migration, cell scatter, and tubulogenesis 1.
In a murine xenograft model of c-Met-dependent gastric cancer, oral administration of MK-2461 at a dosge of 100 mg/kg twice daily effectively inhibited c-Met signaling and tumor growth 1. Consistently, MK-2461 inhibited the tumor growth which was formed by s.c. injection of mouse NIH-3T3 cells expressing oncogenic c-Met mutants 1. These evidence support the preclinical development of MK-2461 for cancer therapy.
Reference:
1. Pan BS, Chan GK, Chenard M, et al. MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer research. 2010;70(4):1524-1533.