Irreversible inhibition of epidermal growth factor receptor activity by 3-aminopropanamides

C Carmi, E Galvani, F Vacondio, S Rivara…

Index: Carmi, Caterina; Galvani, Elena; Vacondio, Federica; Rivara, Silvia; Lodola, Alessio; Russo, Simonetta; Aiello, Stefania; Bordi, Fabrizio; Costantino, Gabriele; Cavazzoni, Andrea; Alfieri, Roberta R.; Ardizzoni, Andrea; Petronini, Pier Giorgio; Mor, Marco Journal of Medicinal Chemistry, 2012 , vol. 55, # 5 p. 2251 - 2264

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Citation Number: 33

Abstract

Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off- targets. We describe here a new series of irreversible inhibitors containing a 3- ...