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Overview
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Background
SU11274 is a potent and selective inhibitor of Met kinase with IC50 value of 10nM [1].
SU11274 shows high selectivity toward Met kinase versus a serine/threonine kinase, cyclin-dependent kinase 2 (CDK2), or other receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFRβ) [1].
SU11274 has revealed to inhibit autophosphorylation of Met at kinase tyrosines 1234/1235 in NIH3T3 cells expressing drug-sensitive or drug-resistant MET mutants and human lung cancer cell line H1993, however, concomitantly, increase total MET levels dose-dependently. Cells treated with SU11274 (2 μM for 16 h) has shown a reduction of Met Ubiquitination [2].[1] Wang X1, Le P, Liang C, Chan J, Kiewlich D, Miller T, Harris D, Sun L, Rice A, Vasile S, Blake RA, Howlett AR, Patel N, McMahon G, Lipson KE. Potent and selective inhibitors of the Met [hepatocyte growth factor/scatter factor (HGF/SF) receptor] tyrosine kinase block HGF/SF-induced tumor cell growth and invasion. Mol Cancer Ther. 2003 Nov;2(11):1085-92.
[2] Leiser D1, Pochon B1, Blank-Liss W1, Francica P1, Glück AA1, Aebersold DM1, Zimmer Y1, Medová M2. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation. FEBS Lett. 2014 Mar 3;588(5):653-8.
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