title: Epidermal growth factor receptor irreversible inhibitors: chemical exploration of the cysteine-trap portion.
abstract: 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.
authors.affiliation: Dipartimento Farmaceutico, Universita degli Studi di Parma, Parma, Italy. caterina.carmi@unipr.it
authors.forename: C
authors.initials: C
authors.lastname: Carmi
authors.forename: A
authors.initials: A
authors.lastname: Lodola
authors.forename: S
authors.initials: S
authors.lastname: Rivara
authors.forename: F
authors.initials: F
authors.lastname: Vacondio
authors.forename: A
authors.initials: A
authors.lastname: Cavazzoni
authors.forename: R R
authors.initials: RR
authors.lastname: Alfieri
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: P G
authors.initials: PG
authors.lastname: Petronini
authors.forename: M
authors.initials: M
authors.lastname: Mor
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D003545:Cysteine