Elkamhawy, Ahmed Farag, Ahmed Karam Viswanath, Ambily Nath Indu Bedair, Tarek M. Leem, Dong Gyu Lee, Kyung-Tae Pae, Ae Nim Roh, Eun Joo 2024-01-20T05:33:19Z 2024-01-20T05:33:19Z 2021-09-03 2015-11-15 0960-894X https://pubs.kist.re.kr/handle/201004/124746 Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazoline core to selectively inhibit EGFR/HER2 tyrosine kinases. Twelve compounds (8a-8d, 9a, 9c, 9d, 10a, 10c, 11b, 14, and 15) showed nanomolar range of IC50 values on EGFR and/or HER2 kinases. Accordingly, a detailed structure activity relationship (SAR) was established. A molecular docking study demonstrated the favorable binding modes of 8d, 9b, 9d and 10d at the ATP active site of both kinases. A kinase selectivity profile performed for compound 8d showed great selectivity for EGFR and HER2. In addition, 8d, 9c, and 9d exerted selective promising cytotoxic activity over BT-474 cell line with IC50 values of 2.70, 1.82 and 1.95 mu M, respectively. From these results, we report analogs 8d, 9c, and 9d as promising candidates for the discovery of well-balanced compounds in terms of the kinase inhibitory potency and antiproliferative activity. (C) 2015 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. GROWTH-FACTOR RECEPTOR LUNG-CANCER MODELS LAPATINIB RESISTANCE DUAL INHIBITORS ACCURATE DOCKING DRUG-RESISTANCE BREAST-CANCER TUMOR-CELLS EGFR ERBB2 Targeting EGFR/HER2 tyrosine kinases with a new potent series of 6-substituted 4-anilinoquinazoline hybrids: Design, synthesis, kinase assay, cell-based assay, and molecular docking Article 10.1016/j.bmcl.2015.10.003 1 Bioorganic & Medicinal Chemistry Letters, v.25, no.22, pp.5147 - 5154 Bioorganic & Medicinal Chemistry Letters 25 22 5147 5154 scie scopus 000364535000026 2-s2.0-84945954062 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article GROWTH-FACTOR RECEPTOR LUNG-CANCER MODELS LAPATINIB RESISTANCE DUAL INHIBITORS ACCURATE DOCKING DRUG-RESISTANCE BREAST-CANCER TUMOR-CELLS EGFR ERBB2 Synthesis EGFR/HER2 dual inhibitors Antiproliferative activity Bt-474 cell line Molecular docking Kinase panel