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|Ref Type||Journal Article|
|Authors||Hardwicke MA, Oleykowski CA, Plant R, Wang J, Liao Q, Moss K, Newlander K, Adams JL, Dhanak D, Yang J, Lai Z, Sutton D, Patrick D|
|Title||GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models.|
|Journal||Molecular cancer therapeutics|
|Abstract Text||The protein kinases, Aurora A, B, and C have critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. GSK1070916, is a novel ATP competitive inhibitor that is highly potent and selective for Aurora B/C kinases. Human tumor cells treated with GSK1070916 show dose-dependent inhibition of phosphorylation on serine 10 of Histone H3, a substrate specific for Aurora B kinase. Moreover, GSK1070916 inhibits the proliferation of tumor cells with EC(50) values of <10 nmol/L in over 100 cell lines spanning a broad range of tumor types. Although GSK1070916 has potent activity against proliferating cells, a dramatic shift in potency is observed in primary, nondividing, normal human vein endothelial cells, consistent with the proposed mechanism. We further determined that treated cells do not arrest in mitosis but instead fail to divide and become polyploid, ultimately leading to apoptosis. GSK1070916 shows dose-dependent inhibition of phosphorylation of an Aurora B-specific substrate in mice and consistent with its broad cellular activity, has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. These results show that GSK1070916 is a potent Aurora B/C kinase inhibitor that has the potential for antitumor activity in a wide range of human cancers.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|GSK1070916||GSK1070916A||Aurkb Inhibitors 18 Aurkc Inhibitors 3||GSK1070916 is a selective inhibitor of Aurora B/C kinases, which induces inhibition of tumor cell proliferation in culture and in xenograft models (PMID: 19567821).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||hematologic cancer||not applicable||GSK1070916||Preclinical - Cell line xenograft||Actionable||In a preclinical study, GSK1070916 inhibited proliferation of a variety of hematological cancer types in cell culture and in xenografts (PMID: 19567821).||19567821|
|Unknown unknown||Advanced Solid Tumor||not applicable||GSK1070916||Preclinical - Cell line xenograft||Actionable||In a preclinical study, GSK1070916 inhibited proliferation of a variety of advanced solid tumors in cell culture and in xenografts (PMID: 19567821).||19567821|