Elkamhawy, Ahmed Ammar, Usama M. Paik, Sora Abdellattif, Magda H. Elsherbeny, Mohamed H. Lee, Kyeong Roh, Eun Joo 2024-01-19T14:01:41Z 2024-01-19T14:01:41Z 2021-10-21 2021-09 1420-3049 https://pubs.kist.re.kr/handle/201004/116547 Recently, multitargeted drugs are considered a potential approach in treating cancer. In this study, twelve in-house indole-based derivatives were preliminary evaluated for their inhibitory activities over VEGFR-2, CDK-1/cyclin B and HER-2. Compound 15l showed the most inhibitory activities among the tested derivatives over CDK-1/cyclin B and HER-2. Compound 15l was tested for its selectivity in a small kinase panel. It showed dual selectivity for CDK-1/cyclin B and HER-2. Moreover, in vitro cytotoxicity assay was assessed for the selected series against nine NCI cell lines. Compound 15l showed the most potent inhibitory activities among the tested compounds. A deep in silico molecular docking study was conducted for compound 15l to identify the possible binding modes into CDK-1/cyclin B and HER-2. The docking results revealed that compound 15l displayed interesting binding modes with the key amino acids in the binding sites of both kinases. In vitro and in silico studies demonstrate the indole-based derivative 15l as a selective dual CDK-1 and HER-2 inhibitor. This emphasizes a new challenge in drug development strategies and signals a significant milestone for further structural and molecular optimization of these indole-based derivatives in order to achieve a drug-like property. English MDPI TYROSINE KINASE INHIBITOR CDK INHIBITORS BIOLOGICAL EVALUATION DESIGN DERIVATIVES GROWTH FLAVOPIRIDOL SELECTIVITY RESISTANCE THERAPY Scaffold Repurposing of In-House Small Molecule Candidates Leads to Discovery of First-in-Class CDK-1/HER-2 Dual Inhibitors: In Vitro and In Silico Screening Article 10.3390/molecules26175324 1 MOLECULES, v.26, no.17 MOLECULES 26 17 scie scopus 000694308600001 2-s2.0-85114344869 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article TYROSINE KINASE INHIBITOR CDK INHIBITORS BIOLOGICAL EVALUATION DESIGN DERIVATIVES GROWTH FLAVOPIRIDOL SELECTIVITY RESISTANCE THERAPY CDK-1 cyclin B HER-2 anti-proliferative anti-cancer molecular docking drug repurposing