{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang LX"],"funding":["NIAAA NIH HHS"],"pagination":["35533"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5099696"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6"],"pubmed_abstract":["The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cell"],"journal":["Scientific reports"],"pubmed_title":["Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation."],"pmcid":["PMC5099696"],"funding_grant_id":["U01 AA020926"],"pubmed_authors":["Hu Y","Lu G","Long ZJ","Liu LL","Wang JD","Wang LX","Chen JJ","Liu Q","Tu XX","Luo Y","Long B","Lin DJ"],"additional_accession":[]},"is_claimable":false,"name":"Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.","description":"The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cell","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2026-05-05T11:53:50.734Z","creation":"2019-03-27T02:28:29Z"},"accession":"S-EPMC5099696","cross_references":{"pubmed":["27824120"],"doi":["10.1038/srep35533"]}}