Biological Activity
nps-1034 is a met inhibitor with ic50 of 4 nmol/l [1].the hepatocyte growth factor receptor tyrosine kinase met is required for various morphogenetic events and controls the malignant progression of many human tumors. in various advanced human cancer, gene amplification can deregulate met [1].in mkn45 and snu638 cell lines highly expressing the met gene and p-met (phosphorylated met), ic50 values of nps-1034 to inhibit cell viability were 112.7 and 190.3 nmol, respectively. in ags, katoiii, nci-n87, mkn1, mkn28, and mkn74 cells, the ic50 values of nps-1034 to inhibit cell viability ranged from 1 μmol to more than 10 μmol. in mkn45 cells, treatment with nps-1034 dramatically decreased met phosphorylation (activation). but in mkn28 cells, met phosphorylation was not dramatically decreased. this meant that the anti-proliferative effect of nps-1034 was resulted from its inhibition of p-met [1].in nude mice bearing mkn45 tumors, after the diameter of mkn45 tumors had reached about 180 mm3, nps-1034 at a dose of 30 mg/kg or pbs as vehicle was orally administered once daily for 25 days. it was found that nps-1034 inhibited the proliferation of tumors highly expressing p-met. without drug treatment, neovascularization appeared in tumors in nude mice when the tumor volume was >150 mm3. nps-1034 treatment clearly decreased the vascularization of the tumors in nude mice [1].
References
[1]. shin js, hong sw, moon jh, et al. nps-1034, a novel met inhibitor, inhibits the activated met receptor and its constitutively active mutants. investigational new drugs, 2014, 32(3): 389-399.
