Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR

Bálint Hegymegi-Barakonyi, Dániel Eros, Csaba Szántai-Kis, Nóra Breza, Péter Bánhegyi, Gábor Viktor Szabó, Edit Várkondi, I. Peták, L. Őrfi, G. Kéri

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Abnormally elevated EGFR kinase activity can lead to various pathological states, including proliferative diseases such as cancer. The development of selective protein kinase inhibitors has become an important area of drug discovery for the potential treatment of a variety of solid tumors such as breast, ovarian and colorectal cancers, NSCLC, and carcinoma of the head and neck. There are three small molecule EGFR kinase inhibitor drugs in clinical use (gefitinib, erlotinib and lapatinib), and several others are currently undergoing clinical development. This review summarizes the development of EGFR kinase inhibitors, and includes descriptions of the binding modes, the importance of a multiple-targets strategy, the effects of sensitizing and resistance mutations in the EGFR, and molecular diagnostic approaches. In addition, the use of target fishing for selectivity profiling, off-target identification and quantitative structure-activity relationship modeling for the prediction of EGFR inhibition is discussed.

Original languageEnglish
Pages (from-to)308-321
Number of pages14
JournalCurrent Opinion in Molecular Therapeutics
Volume11
Issue number3
Publication statusPublished - Jun 2009

Fingerprint

Protein-Tyrosine Kinases
Phosphotransferases
Molecular Weight
Colorectal Neoplasms
Quantitative Structure-Activity Relationship
Molecular Pathology
Drug Discovery
Protein Kinase Inhibitors
Ovarian Neoplasms
Neoplasms
Neck
Head
Breast Neoplasms
Mutation
Pharmaceutical Preparations
gefitinib
lapatinib
Erlotinib Hydrochloride

Keywords

  • EGFR
  • EGFR kinase inhibitor
  • Multiple targets
  • Signal transduction

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery
  • Pharmacology

Cite this

Hegymegi-Barakonyi, B., Eros, D., Szántai-Kis, C., Breza, N., Bánhegyi, P., Szabó, G. V., ... Kéri, G. (2009). Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR. Current Opinion in Molecular Therapeutics, 11(3), 308-321.

Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR. / Hegymegi-Barakonyi, Bálint; Eros, Dániel; Szántai-Kis, Csaba; Breza, Nóra; Bánhegyi, Péter; Szabó, Gábor Viktor; Várkondi, Edit; Peták, I.; Őrfi, L.; Kéri, G.

In: Current Opinion in Molecular Therapeutics, Vol. 11, No. 3, 06.2009, p. 308-321.

Research output: Contribution to journalArticle

Hegymegi-Barakonyi, B, Eros, D, Szántai-Kis, C, Breza, N, Bánhegyi, P, Szabó, GV, Várkondi, E, Peták, I, Őrfi, L & Kéri, G 2009, 'Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR', Current Opinion in Molecular Therapeutics, vol. 11, no. 3, pp. 308-321.
Hegymegi-Barakonyi B, Eros D, Szántai-Kis C, Breza N, Bánhegyi P, Szabó GV et al. Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR. Current Opinion in Molecular Therapeutics. 2009 Jun;11(3):308-321.
Hegymegi-Barakonyi, Bálint ; Eros, Dániel ; Szántai-Kis, Csaba ; Breza, Nóra ; Bánhegyi, Péter ; Szabó, Gábor Viktor ; Várkondi, Edit ; Peták, I. ; Őrfi, L. ; Kéri, G. / Tyrosine kinase inhibitors - Small molecular weight compounds Inhibiting EGFR. In: Current Opinion in Molecular Therapeutics. 2009 ; Vol. 11, No. 3. pp. 308-321.
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