Thitinan AiebchunPanupong MahalapbutrAtima AuepattanapongOnnicha KhaikateSupaphorn SeetahaLueacha TabtimmaiChutima KuhakarnKiattawee ChoowongkomonThanyada RungrotmongkolKing Mongkuts University of TechnologyChulalongkorn UniversityFaculty of Medicine, Khon Kaen UniversityKasetsart UniversityMahidol University2022-08-042022-08-042021-01-01Molecules. Vol.26, No.8 (2021)142030492-s2.0-85105164646https://repository.li.mahidol.ac.th/handle/20.500.14594/76380Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC50 value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC50 values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.3390/molecules26082211