Zaraei, Seyed-Omar Sbenati, Rawan M. Alach, Nour N. Anbar, Hanan S. El-Gamal, Randa Tarazi, Hamadeh Shehata, Mahmoud K. Abdel-Maksoud, Mohammed S. Oh, Chang-Hyun El-Gamal, Mohammed, I 2024-01-19T13:30:38Z 2024-01-19T13:30:38Z 2022-01-10 2021-11-15 0223-5234 https://pubs.kist.re.kr/handle/201004/116127 This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. There are no other reported selective inhibitors of this kinase in the literature, that's why they are considered as first-in-class. In addition, none of the reported non-selective ErbB4 inhibitors possesses imidazothiazole nucleus in its structure. Therefore, there is novelty in this work in both kinase selectivity and chemical structure. Compounds Ik and IIa are the most potent ErbB4 kinase inhibitor (IC50 = 15.24 and 17.70 nM, respectively). Compound Ik showed promising antiproliferative activity. It is selective towards cancer cell lines than normal cells. Its ability to penetrate T-47D cell membrane and inhibit ErbB4 kinase inside the cells has been confirmed. Moreover, both compound Ik and IIa have additional merits such as weak potency against hERG ion channels and against CYP 3A4 and 2D6. Molecular docking and dynamic simulation studies were carried out to explain binding interactions. (C) 2021 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER GROWTH-FACTOR RECEPTOR IN-VITRO CANCER DERIVATIVES MECHANISM ISOFORMS DESIGN FAMILY Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors Article 10.1016/j.ejmech.2021.113674 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.224 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 224 scie scopus 000703110000006 2-s2.0-85109070443 Chemistry, Medicinal Pharmacology & Pharmacy Article GROWTH-FACTOR RECEPTOR IN-VITRO CANCER DERIVATIVES MECHANISM ISOFORMS DESIGN FAMILY Antiproliferative ErbB4 HER4 Imidazo[2,1-b]thiazole Kinase inhibitor