NPS-1034 serves as a dual antagonist for AXL and MET, exhibiting IC50 values of 10.3 nM for AXL and 48 nM for MET. In HCC827/ER cells, where AXL's expression and activity are notably heightened, treatment with NPS-1034 successfully curtails its tyrosine phosphorylation. NPS-1034 reduces the viability of MKN45 and SNU638 cell lines, which have high expression levels of the MET gene and phosphorylated MET, with IC50 values of 112.7 nM and 190.3 nM, respectively. Conversely, it inhibits the viability of AGS, KATOIII, NCI-N87, MKN1, MKN28, and MKN74 cell lines with IC50 values ranging from 1 μM to over 10 μM. Treatment with NPS-1034 significantly lowers MET phosphorylation in MKN45 cells, but not in MKN28 cells. It also inhibits HGF-induced MET autophosphorylation in AGS and MKN1 cell lines with IC50 values of less than 10 nM and less than 50 nM, respectively, with 50 nM of NPS-1034 completely blocking HGF-induced MET phosphorylation[1].
NPS-1034 动物研究
Animal study
NPS-1034 suppresses tumor growth in tumors that express high levels of phosphorylated MET and leads to a notable reduction in tumor vascularization. The expression of α-SMA is also reduced in the tumor sections of mice treated with NPS-1034. Mice treated with NPS-1034 exhibit no significant weight loss, suggesting that the compound is generally well-tolerated[2].
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