Cheng H.-W.Chein R.-J.Cheng T.-J.Wu P.-S.Wu H.-Y.Hung P.-F.Wang C.-J.Hsu Y.-L.Wong J.-M.ANG YUANWong C.-H.PAN-CHYR YANGSZU-HUA PAN2021-06-042021-06-0420181347-9032https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041635556&doi=10.1111%2fcas.13489&partnerID=40&md5=4cb57f0d689e0969bf8b21193eb309eehttps://scholars.lib.ntu.edu.tw/handle/123456789/565092Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents has become critical for lung cancer treatment. In this study, compound AS7128 was selected from a 2-million entry chemical library screening and identified as a candidate drug against non-small cell lung cancer in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and, thus, increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs through disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insight for using iASPP as a therapeutic target for non-small cell lung cancer treatment. ? 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.[SDGs]SDG32 anilino 4 amino 5 aroylthiazole; alanine aminotransferase; antineoplastic agent; apoptosis stimulating protein of p53; as 7128; aspartate aminotransferase; beta actin; caspase 3; creatinine; cyclin A; cyclin B1; cyclin D1; cyclin dependent kinase 2; cyclin E; histone H3; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; nitrogen; protein; protein p53; thiazole derivative; unclassified drug; antineoplastic agent; AS7128; PPP1R13L protein, human; protein binding; protein p53; repressor protein; signal peptide; thiazole derivative; TP53 protein, human; animal experiment; animal model; animal tissue; apoptosis; Article; cancer inhibition; controlled study; drug identification; drug mechanism; drug protein binding; drug screening; G1 phase cell cycle checkpoint; G2 phase cell cycle checkpoint; gene targeting; human; human cell; in vitro study; in vivo study; M phase cell cycle checkpoint; mitosis; mouse; non small cell lung cancer; nonhuman; priority journal; protein expression; protein interaction; transactivation; A-549 cell line; animal; cell proliferation; cell survival; drug effects; gene expression regulation; lung tumor; metabolism; non small cell lung cancer; tumor cell line; A549 Cells; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Mice; Protein Binding; Repressor Proteins; Thiazoles; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assaysjournal article10.1111/cas.13489292858472-s2.0-85041635556