Epidermal Growth Factor Receptor Irreversible Inhibitors: Chemical Exploration of the Cysteine-Trap Portion

被引：36

作者：

Carmi, C. ^{[1
]}

Lodola, A. ^{[1
]}

Rivara, S. ^{[1
]}

Vacondio, F. ^{[1
]}

Cavazzoni, A. ^{[2
]}

Alfieri, R. R. ^{[2
]}

Ardizzoni, A. ^{[3
]}

Petronini, P. G. ^{[2
]}

Mor, M. ^{[1
]}

机构：

[1] Univ Parma, Dipartimento Farmaceut, I-43124 Parma, Italy

[2] Univ Parma, Dipartimento Med Sperimentale, I-43125 Parma, Italy

[3] Azienda Osped Univ Parma, I-43126 Parma, Italy

来源：

MINI-REVIEWS IN MEDICINAL CHEMISTRY | 2011年 / 11卷 / 12期

关键词：

Antitumor; covalent inhibition; cysteine-trap; EGFR; erbB receptors; irreversible inhibitors; NSCLC; TYROSINE KINASE INHIBITORS; CELL LUNG-CANCER; PHASE-I; ACQUIRED-RESISTANCE; COVALENT MODIFIERS; EGF RECEPTOR; MECHANISMS; MUTATIONS; AFFINITY; DESIGN;

D O I：

10.2174/138955711797247725

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Covalent EGFR irreversible inhibitors showed promising potential for the treatment of gefitinib-resistant tumors and for imaging purposes. They contain a cysteine-reactive portion forming a covalent bond with the protein. Irreversible kinase inhibitors have been advanced to clinical studies, mostly characterized by an acrylamide or butynamide warhead. However, the clinical usefulness of these compounds has been hampered by resistances, toxicity and pharmacokinetic problems. Investigation on the structure-activity and structure-reactivity relationships may provide useful information for compounds with improved selectivity and pharmacokinetic properties. This review focuses on the exploration of the cysteine-trap portions able to irreversibly inhibit EGFR and other erbB receptors.

引用

页码：1019 / 1030

页数：12

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