Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge


Recent Advances in Drug Design of Epidermal Growth Factor Receptor Inhibitors

Author(s): P. Warnault, A. Yasri, M. Coisy-Quivy, G. Cheve, C. Bories, B. Fauvel and R. Benhida

Affiliation: Equipe Molecules Bioactives, Institut de Chimie de Nice, UMR UNS CNRS 7272. Universite de Nice Sophia Antipolis. Parc Valrose, 06108 Nice cedex 2. France.

Keywords: Breast cancer, drug design, EGFR, irreversible inhibitors, NSCLC, mutation, reversible inhibitors


The tyrosine kinase epidermal growth factor receptor (EGFR) has emerged in recent years as a key and validated target of targeted therapies for solid tumors. It plays a central role in oncology since it is involved in many steps of tumor progression such as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of differentiation. Recent advances in targeted therapies have demonstrated that tyrosine kinase inhibitors (TKIs), have provided a marked benefit to subsets of patients whose tumors harbor specific genetic abnormalities. However, resistance phenomenon appears rapidly and patients with EGFR mutations acquire resistance to TKI inhibitors decreasing therefore the median time to disease progression to few months. Several strategies were envisioned to overcome this resistance, such as dual–target inhibitors, multitarget and combined therapy. This review summarizes recent advances in TKIs development with special focus on rational strategies for the design of potent EGFR inhibitors including molecular modeling studies based on crystallographic data. Such advances open the way for new research possibilities in modern medicinal chemistry combined to structure-based drug design.

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Article Details

Page: [2043 - 2067]
Pages: 25
DOI: 10.2174/0929867311320160001