EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata

Translated title of the contribution: Development and biochemical characterization of EGFR/c-Met dual inhibitors

Szokol Bálint, Gyulavári Ṕal, Baska Ferenc, Ibolya Kurkó, Greff Zoltán, Szántai Kis-Csaba, Zoltán Orfi, I. Peták, Axel Ullrich, T. Vántus, G. Kéri, L. Őrfi

Research output: Contribution to journalArticle

Abstract

The epidermal growth factor receptor (EGFR) family has been well-known for more than ten years as the target of non-small lung carcinoma (NSCLC) which is one of the leading cause of mortality among the cancer types. The receptor tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib) which have been applied in the therapy, are not able to inhibit the progression of this disease perfectly because of resistance. It has been demonstrated that the amplification of mesenchymal-epithelial transition factor (c-Met) or secondary mutation of EGFR kinase causes the resistance against EGFR inhibitors in 18-20 percent of the cases. Clinical candidates inhibiting both of EGFR and c-Met kinases are unknown in the literature. We have developed quinoline-based inhibitors in our research project, which inhibit both kinases in submicromolar range in enzymatic assays, moreover we have demonstrated by western blot analysis that these compounds inhibit the autophosphorylation in vivo. The binding of the effective compounds was examined by in silico and docking simulations.

Original languageHungarian
Pages (from-to)121-133
Number of pages13
JournalActa Pharmaceutica Hungarica
Volume83
Issue number4
Publication statusPublished - 2013

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Epidermal Growth Factor Receptor
Phosphotransferases
Epithelial-Mesenchymal Transition
Enzyme Assays
Receptor Protein-Tyrosine Kinases
Computer Simulation
Disease Progression
Western Blotting
Carcinoma
Lung
Mutation
Mortality
Research
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Bálint, S., Ṕal, G., Ferenc, B., Kurkó, I., Zoltán, G., Kis-Csaba, S., ... Őrfi, L. (2013). EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata. Acta Pharmaceutica Hungarica, 83(4), 121-133.

EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata. / Bálint, Szokol; Ṕal, Gyulavári; Ferenc, Baska; Kurkó, Ibolya; Zoltán, Greff; Kis-Csaba, Szántai; Orfi, Zoltán; Peták, I.; Ullrich, Axel; Vántus, T.; Kéri, G.; Őrfi, L.

In: Acta Pharmaceutica Hungarica, Vol. 83, No. 4, 2013, p. 121-133.

Research output: Contribution to journalArticle

Bálint, S, Ṕal, G, Ferenc, B, Kurkó, I, Zoltán, G, Kis-Csaba, S, Orfi, Z, Peták, I, Ullrich, A, Vántus, T, Kéri, G & Őrfi, L 2013, 'EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata', Acta Pharmaceutica Hungarica, vol. 83, no. 4, pp. 121-133.
Bálint S, Ṕal G, Ferenc B, Kurkó I, Zoltán G, Kis-Csaba S et al. EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata. Acta Pharmaceutica Hungarica. 2013;83(4):121-133.
Bálint, Szokol ; Ṕal, Gyulavári ; Ferenc, Baska ; Kurkó, Ibolya ; Zoltán, Greff ; Kis-Csaba, Szántai ; Orfi, Zoltán ; Peták, I. ; Ullrich, Axel ; Vántus, T. ; Kéri, G. ; Őrfi, L. / EGFR/c-Met ketto{combining double acute accent}sgátlók fejlesztése és biokémiai vizsgálata. In: Acta Pharmaceutica Hungarica. 2013 ; Vol. 83, No. 4. pp. 121-133.
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