|CAS No.||722544-51-6||Synonyms||INH 34|
|Solubility (25°C) *||In vitro||DMSO||102 mg/mL (200.96 mM)|
|Ethanol||3 mg/mL (5.91 mM)|
|In vivo||2% DMSO+40% PEG 300+2% Tween 80+ddH2O||7mg/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).
Kinase-controlled phase transition of membraneless organelles in mitosis [Rai AK, et al. Nature, 2018, 559(7713):211-216]PubMed: 29973724
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
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
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
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
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
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
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