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Ref Type Journal Article
PMID (19567821)
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
Vol 8
Issue 7
Date 2009 Jul
URL
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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
GSK1070916 GSK1070916 2 0
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