title: Computer-aided identification of novel anticancer compounds with a possible dual HER1/HER2 inhibition mechanism.
abstract: HER1 and HER2 are frequently overexpressed in human tumors where they drive cellular proliferation. For this reason they are considered important targets in anticancer therapy with dual HER1/HER2 inhibitors being recently approved and marketed. In this paper we report the identification of a series of compounds with anticancer activity by a combined virtual screening approach on the kinase domains of HER1 and HER2. 6 hit compounds that present a sub- or low-micromolar activity in two cell-based assays, were initially identified and a subsequent design cycle led to the synthesis of a compound with nanomolar activity in the cell-based assays.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII avenue, Cardiff CF10 3NB, UK; Green Chemistry Department, National Research Centre, Cairo, Egypt. Electronic address: AliS30@cardiff.ac.uk.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Elseginy
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII avenue, Cardiff CF10 3NB, UK.
authors.forename: Glorianne
authors.initials: G
authors.lastname: Lazaro
authors.affiliation: Green Chemistry Department, National Research Centre, Cairo, Egypt.
authors.forename: Galal A M
authors.initials: GA
authors.lastname: Nawwar
authors.affiliation: Department of Pharmaceutical Chemistry, Cairo University, Cairo, Egypt.
authors.forename: Kamilia M
authors.initials: KM
authors.lastname: Amin
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII avenue, Cardiff CF10 3NB, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hiscox
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII avenue, Cardiff CF10 3NB, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017076:Computer-Aided Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005260:Female; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: HER1 EGFR; HER2; Virtual screening structure-based drug design