|-- -- --|
|Solubility (25°C) *||In vitro||DMSO||102 mg/mL (200.96 mM)|
|Ethanol||3 mg/mL (5.91 mM)|
|In vivo||2% DMSO+30% PEG 300+ddH2O||5mg/mL|
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
|Description||Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.|
|In vitro||AZD1152 displays >3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 μM. AZD1152 has even less activity against 50 other serine-threonine and tyrosine kinases including FLT3, JAK2, and Abl. AZD1152 inhibits the proliferation of hematopoietic malignant cells such as HL-60, NB4, MOLM13, PALL-1, PALL-2, MV4-11, EOL-1, THP-1, and K562 cells with IC50 of 3-40 nM, displaying ~100-fold potency than another Aurora kinase inhibitor ZM334739 which has IC50 of 3-30 μM. AZD1152 inhibits the clonogenic growth of MOLM13 and MV4-11 cells with IC50 of 1 nM and 2.8 nM, respectively, as well as the freshly isolated imatinib-resistant leukemia cells with IC50 values of 1-3 nM, more significantly compared with bone marrow mononuclear cells with IC50 values of >10 nM. AZD1152 induces accumulation of cells with 4N/8N DNA content, followed by apoptosis in a dose- and time-dependent manner. |
|In vivo||Administration of AZD1152 (25 mg/kg) alone markedly suppresses the growth of MOLM13 xenografts, confirmed by the observation of necrotic tissue with infiltration of phagocytic cells.  In addition, AZD1152 (10-150 mg/kg/day) significantly inhibits the growth of a variety of human solid tumor xenografts, including colon, breast, and lung cancers, in a dose-dependent manner. |
|Cell lines||HL-60, NB4, MOLM13, PALL-2, MV4-11, EOL-1, and K562 cells|
|Concentrations||Dissolved in DMSO, final concentrations ~100 nM|
|Incubation Time||24 or 48 hours|
|Method||Cells are exposed to various concentrations of AZD1152 for 24 or 48 hours. Cell proliferation is measured by 3H-thymidine uptake (isotope added 6 hours before harvest), and the concentration that induced 50% growth inhibition (IC50) is calculated from dose-response curves. Cell cycle analysis is performed by flow cytometry. Cell apoptosis is measured by annexin V–FITC apoptosis detection kit.|
|Animal Models||Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells|
|Formulation||Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL|
|Dosages||5 or 25 mg/kg|
|Administration||Intraperitoneal injection 4 times a week or every another day|
Data from [Data independently produced by Nature, 2014, 508(7494), 118-22]
Targeting PI3K, a common downstream effector of RTKs, with a selective inhibitor (GDC0941) sensitizes SOX10 knockdown cells to vemurafenib. shRNAs targeting SOX10 were introduced into A375 cells by lentiviral transduction. pLKO.1 empty vector served as a control vector (Ctrl). Cells were seeded in 6-well plates at the same density in the presence or absence of drug(s) at the indicated concentration. Cells were cultured for 2 weeks in the absence of vemurafenib or 4 weeks in the presence of vemurafenib before fixing and staining.
Data from [Data independently produced by J Exp Med, 2014, 10.1084/jem.20141123]
Primary MKPs were treated with the Aurora B inhibitor AZD-1152, and then stimulated with 20 ng/ml TPO for 5 d. Cell morphology was analyzed by Giemsa staining (Bar, 20 祄; red arrows denote mature MKs; n = 6).
ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4. [Thoresen SB, et al. Nat Cell Biol, 2014, 16(6):550-60]PubMed: 24814515
Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation. [Ye B, et al. J Exp Med, 2014, 211(12):2439-54]PubMed: 25332286
A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases. [Tanenbaum ME, et al. Curr Biol, 2011, 21(16):1356-65]PubMed: 21820309
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res, 2013, 73(20):6310-22]PubMed: 24067506
System-level analysis of neuroblastoma tumor-initiating cells implicates AURKB as a novel drug target for neuroblastoma. [Morozova O, et al. Clin Cancer Res, 2010, 16(18):4572-82]PubMed: 20651058
p53 deficiency enhances mitotic arrest and slippage induced by pharmacological inhibition of Aurora kinases. [Marxer M, et al. Oncogene, 2014, 33(27):3550-60]PubMed: 23955083
Synergistic Activities of MET/RON Inhibitor BMS-777607 and mTOR Inhibitor AZD8055 to Polyploid Cells Derived from Pancreatic Cancer and Cancer Stem Cells. [Zeng JY, et al. Mol Cancer Ther, 2013, 13(1):37-48]PubMed: 24233399
Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins [Boeckx C,et al. Cancer Lett, 2014, 354(2):365-77]PubMed: 25192874
MicroRNA let-7b regulates genomic balance by targeting Aurora B kinase. [Maki-Jouppila JHE, et al. Mol Oncol, 2015, 10.1016/j.molonc.2015.01.005]PubMed: 25682900
Sequential treatment with aurora B inhibitors enhances cisplatin-mediated apoptosis via c-Myc. [Ma Y, et al. J Mol Med, 2015, 93(4):427-38]
DNA replication stress in CHK1-depleted tumour cells triggers premature (S-phase) mitosis through inappropriate activation of Aurora kinase B. [Zuazua-Villar P, et al. Cell Death Dis, 2014, 5:e1253]PubMed: 24853431
Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death [Chen H et al. Cell Death Dis, 2014, 5:e1177]PubMed: 24743732
Dependency of 2-methoxyestradiol-induced mitochondrial apoptosis on mitotic spindle network impairment and prometaphase arrest in human Jurkat T cells. [Lee ST, et al. Biochem Pharmacol, 2015, 10.1016/j.bcp.2015.02.011]PubMed: 25732194
Localized Aurora B activity spatially controls non-kinetochore microtubules during spindle assembly. [Tanenbaum ME, et al. Chromosoma, 2011, 120(6):599-607]PubMed: 21786106
Aurora B interacts with NIR-p53, leading to p53 phosphorylation in its DNA-binding domain and subsequent functional suppression. [Wu L, et al. J Biol Chem, 2011, 286(3):2236-44]PubMed: 20959462
The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent. [Nair JS, et al. Cell Cycle, 2012, 11(4):807-17]PubMed: 22293494
Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells. [Hole S, et al. Breast Cancer Res Tr, 2015, 149(3):715-26]PubMed: 25667100
Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer. [Larsen SL, et al. BMC Cancer, 2015, 10.1186/s12885-015-1210-4]
Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors. [Cannon CM, et al. Vet Comp Oncol, 2013, 10.1111/vco.12018]PubMed: 23410058
Structure of Aurora B-INCENP in complex with barasertib reveals a potential transinhibitory mechanism [Sessa F et al. Acta Crystallogr F Struct Biol Commun, 2014, 70(Pt 3):294-8]PubMed: 24598913
Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy. [Noguchi K, et al. J Biol Chem, 2017, 292(5):1910-1924]PubMed: 28028179
Molecular Characterization of the Induction of Cell Cycle Inhibitor p21 in Response to Inhibition of the Mitotic Kinase Aurora B [Kumari G, et al. Julius Maximilians Universit, 2014, Kumari G]
Prometaphase arrest-dependent phosphorylation of Bcl-2 family proteinsand activation of mitochondrial apoptotic pathway are associated with 17α-estradiol-induced apoptosis in human Jurkat T cells. [Han CR, et al. Biochim Biophys Acta, 2013, 1833(10):2220-32]PubMed: 23707954
Aurora kinase B/C inhibition impairs malignant glioma growth in vivo. [Diaz RJ, et al. J Neurooncol, 2012, 108(3):349-60]PubMed: 22382783
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