Abstract:
:Activating mutations in the epidermal growth factor receptor (EGFR) have been identified in a subset of non-small cell lung cancer (NSCLC), which is one of the leading cancer types worldwide. Application of EGFR tyrosine kinase inhibitors leads to acquired resistance by secondary EGFR mutations or by amplification of the hepatocyte growth factor receptor (c-Met) gene. Although several EGFR and c-Met inhibitors have been reported, potent dual EGFR/c-Met inhibitors, which can overcome this latter resistance mechanism, have hitherto not been published and have not reached clinical trials. In the present study we have identified dual EGFR/c-Met inhibitors and designed novel N-[4-(quinolin-4-yloxy)-phenyl]-biarylsulfonamide derivatives, which inhibit the c-Met receptor and both the wild-type and the activating mutant EGFR kinases in nanomolar range. We have demonstrated by Western blot analysis that compound 10 inhibits EGFR and c-Met phosphorylation at cellular level and effectively inhibits viability of the NSCLC cell lines.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Szokol B,Gyulavári P,Kurkó I,Baska F,Szántai-Kis C,Greff Z,Orfi Z,Peták I,Pénzes K,Torka R,Ullrich A,Orfi L,Vántus T,Kéri Gdoi
10.1021/ml4003309subject
Has Abstractpub_date
2014-01-30 00:00:00pages
298-303issue
4issn
1948-5875journal_volume
5pub_type
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