Cell experiment:

GTL-16 cells are inoculated in to 96 well microtiter plates in 0.5% fetal calf serum and incubated at 37℃, 5% CO2, 95% air and 100% relative humidity for 24 h prior to addition of a compound. Cells are treated with BMS-794833 for an additional 72 h. Growth inhibition is calculated[1].

BMS-794833 is a potent ATP competitive, dual inhibitor of c-Met and VEGFR2 (IC50 = 1.7 nM and 15 nM, respectively). It also has inhibitory effect on Ron, Axl and Flt3 (IC50< 3 nM).

c-MET, also called MET, is a membrane receptor that is essential for embryonic development and wound healing. VEGFR are receptors for vascular endothelial growth factor and belong to receptor tyrosine kinases. It mediates in various cellular functions, including endothelial proliferation, migration, survival, tubular morphogenesis and sprouting. [1]

BMS794833 also inhibited gastric cancer cell line (GTL-16) that induced by c-Met receptor, GTL-16, IC50 = 39 Nm [1]. In human gastric tumor xenografts model, BM798433 exhibits >50% TGI for at least one tumor doubling time without significant toxicity in 14 days. In U87 glioblastoma model, 25mg/kg of BMS798433 exert complete tumor stasis. [1]

Reference:
[1] 4-pyridinone compounds and their use of cancer, Borzilleri et al, United States patent application publication, Pub No. : US 2012/0114643 A1, Pub.Date: May 10, 2012.