TAK-901 is a novel inhibitor of Aurora A and Aurora B with IC50 of 21 nM and 15 nM, respectively.
Targets
Aurora A-TPX2
IC50
21 nM
In Vitro
TAK-901 inhibits Aurora A-TPX2 and Aurora B-INCENP in tight binding, time-dependent manner. Dissociation of TAK-901 from Aurora B-INCENP is slow with at 1/2 of 920 minutes, and the affinity constant for TAK-901 binding to Aurora B-INCENP is determined to be 0.02 nM. TAK-901 induces inhibition of cell proliferation in cultured human cancer cell lines from different tissues with IC50s ranging from 40 to 500nM. Consistent with Aurora B inhibition, TAK-901 treatment produces polyploidy in human PC3 prostate cancer and HL60 acute myeloid leukemia cells as measured by immunofluorescence and flow cytometry. Examination of a broad panel of kinases reveals that multiple kinases, including FLT3, FGFR and the Src family kinases, are inhibited by TAK-901 with IC50 values similar to those for Aurora A and B. In cells, TAK-901 suppresses the Flt3 and FGFR2 autophosphorylation with IC50 values close to that of Aurora B as measured by cellular histone H3 phosphorylation, whereas the IC50s for inhibition of cellular Src and Bcr Abl are 20-fold weaker. In a panel of pathway specific reporter-based cell models, TAK-901 inhibits the NFkB and JAK/STAT pathways with submicromolar potency. [1]
In Vivo
Clinical Trials
TAK-901 is now under the Phase 1 clinical trial for the dose escalation in subjects with advanced hematologic malignancies.
A novel Aurora B kinase inhibitor with potential antineoplastic activity. It binds to and inhibits the activity of Aurora B, which may result in a decrease in the proliferation of tumor cells that overexpress Aurora B. Aurora B is a positive regulator of
References
PubChem Literature
From Data Sources
• Pamela Farrell, et al, AACR, 2009, Abstract B270
