Chao M.-W.Lin T.E.HuangFu W.-C.Chang C.-D.Tu H.-J.Chen L.-C.Yen S.-C.Sung T.-Y.Huang W.-J.CHIA-RON YANGPan S.-L.Hsu K.-C.2021-06-042021-06-04202114756366https://www.scopus.com/inward/record.uri?eid=2-s2.0-85095776883&doi=10.1080%2f14756366.2020.1843452&partnerID=40&md5=1546f6942d20a29ded286cdb6b94795fhttps://scholars.lib.ntu.edu.tw/handle/123456789/565262The STE20 kinase family is a complex signalling cascade that regulates cytoskeletal organisation and modulates the stress response. This signalling cascade includes various kinase mediators, such as TAOK1 and MAP4K5. The dysregulation of the STE20 kinase pathway is linked with cancer malignancy. A small-molecule inhibitor targeting the STE20 kinase pathway has therapeutic potential. In this study, a structure-based virtual screening (SBVS) approach was used to identify potential dual TAOK1 and MAP4K5 inhibitors. Enzymatic assays confirmed three potential dual inhibitors (>50% inhibition) from our virtual screening, and analysis of the TAOK1 and MAP4K5 binding sites indicated common interactions for dual inhibition. Compound 1 revealed potent inhibition of colorectal and lung cancer cell lines. Furthermore, compound 1 arrested cancer cells in the G0/G1 phase, which suggests the induction of apoptosis. Altogether, we show that the STE20 signalling mediators TAOK1 and MAP4K5 are promising targets for drug research. ? 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.cancer; drug discovery; kinase inhibitor; small-molecule; STE20 pathway; Structure-based virtual screening[SDGs]SDG3antineoplastic agent; axitinib; dasatinib; gefitinib; imatinib; kinase homologous to ste20; palbociclib; pazopanib; protein serine threonine kinase; protein serine threonine kinase inhibitor; sunitinib; thousand and one amino acid kinase; unclassified drug; antineoplastic agent; MAP4K5 protein, human; protein kinase inhibitor; protein serine threonine kinase; TAO1 protein kinase; antineoplastic activity; antiproliferative activity; apoptosis; Article; cancer growth; cell cycle G1 phase; cell cycle progression; cell proliferation; cell survival; cell viability; colorectal cancer; controlled study; crystal structure; drug binding site; drug identification; drug protein binding; drug purity; drug screening; drug selectivity; drug targeting; enzyme inhibition; flow cytometry; fluorescence resonance energy transfer; high performance liquid chromatography; high throughput screening; human; human cell; hydrogen bond; IC50; in vitro study; in vivo study; molecular docking; molecular weight; non small cell lung cancer; percentage of cells in G0/G1 phase; priority journal; structure activity relation; cell cycle; chemical structure; chemistry; dose response; drug effect; drug screening; metabolism; preclinical study; structure activity relation; synthesis; tumor cell culture; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Protein Kinase Inhibitors; Protein-Serine-Threonine Kinases; Structure-Activity Relationship; Tumor Cells, Culturedjournal article10.1080/14756366.2020.1843452331677272-s2.0-85095776883