Biological Activity
nvp-bvu972 is a selective and potent inhibitor of c-met with ic50 of 14 nm. besides, nvp-bvu972 displays ic50 values more than 1000 nm in other kinases such as the most closely related kinase recepteur d'origine nantais (ron).c-met, also known as hepatocyte growth factor receptor, is a receptor tyrosine kinase that can be activated by hepatocyte growth factor/scatter factor (hgf/sf). it is a membrane protein which plays an essential role in embryonic development and wound healing.in the ebc-1, gtl-16, and mkn-45 human cancer cells, nvp-bvu972 potently inhibits the cell proliferation with ic50 values of 82, 66 and 32 nm, respectively. additionally, nvp-bvu972 treatment leads to the inhibition of the growth of the transformed mouse baf3 cells containing tpr-met kinase fusions with ic50 of 104 nm 1.in human sample, nvp-bvu972 treatment on cells expressing wild-type tpr-met resulted in a dose-dependent reduction in tpr-met phosphorylation. y1230h, d1228a, f1200i and l1195v mutations abrogate the tpr-met phosphorylation inhibition effect of nvp-bvu972 in baf3 tpr-met1.
References
1. tiedt r, degenkolbe e, furet p, et al. a drug resistance screen using a selective met inhibitor reveals a spectrum of mutations that partially overlap with activating mutations found in cancer patients. cancer research. 2011;71(15):5255-5264.
