Item no. |
S1147-10000 |
Manufacturer |
Selleckchem
|
CASRN |
722544-51-6 |
Amount |
10 g |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
AZD2811, INH-34, Barasertib-HQPA , Defosbarasertib, Aurora B;Aurora Kinase |
Similar products |
Barasertib |
Available |
|
Administration |
Intraperitoneal injection 4 times a week or every another day |
Animal Models |
Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells |
Cell lines |
HL-60, NB4, MOLM13, PALL-2, MV4-11, EOL-1, and K562 cells |
Chemical Name |
2-(5-(7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-ylamino)-1H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide |
Clinical Trials |
A Phase I study to assess the safety and tolerability of AZD1152-HQPA in combination with low dose cytosine arabinoside (LDAC) in patients with acute myeloid leukaemia (AML) has been completed. |
Concentrations |
Dissolved in DMSO, final concentrations ca.100 nM |
Description |
AZD1152-HQPA (Barasertib) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM. |
Dosages |
5 or 25 mg/kg |
Formulation |
Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL |
IC50 |
0.37 nM [1], 0.37 nM [1], 0.37 nM [1], 0.37 nM [1], 0.37 nM [1], 0.37 nM [1] |
In vitro |
AZD1152 displays >3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 uM. 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 ca.100-fold potency than another Aurora kinase inhibitor ZM334739 which has IC50 of 3-30 uM. 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. [1] |
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. [1] 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. [2] |
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. |
Molecular Weight (MW) |
507, 56 |
Picture ChemicalStructure Description |
Barasertib (AZD1152-HQPA) Chemical Structure |
Picture Description 1 |
Data from [Clin Cancer Res , 2010, 16, 4572-4582], Barasertib (AZD1152-HQPA)purchased from Selleck, The alamarBlue assay revealed that AURKB inhibition with AZD1152 was effective in NB TICs at EC50 of 1.5 to 4.6 mol/L, whereas AURKB inhibition was effective in SKPs at 12.4 mol/L. |
Picture Description 2 |
Data from [J Biol Chem , 2011, 286, 2236-44], Barasertib (AZD1152-HQPA)purchased from Selleck, p53 phosphorylation by Aurora B. A, p53 reporter construct was co-transfected with the indicated plasmids into H1299 cells and reporter activation was determined as described under Experimental Procedures. B, U2OS cells and H1299 cells were treated with AZD1152 (AZD) for 12 h at the indicated doses. Cell lysates were harvested and immunoblotted with Bax and actin antibodies. C, U2OS cells were treated with 100 ng/ml nocodazole (noc) overnight, and then shake off cells were harvested, washed with PBS, and reseeded. Approximately 2 h later, cells were either lysated or treated with dimethyl sulfoxide (DMSO) or AZD1152 for another 16 h before harvesting. Cell lysates were immunoblotted with Bax, phospho-H3, and actin antibodies. D, GST-p53 or GST control proteins were incubated with Aurora B protein and analyzed for phosphate incorporation (left panel). Coomassie staining of GSTp53 and GST protein is also shown (right panel). E, In vitro phosphorylation sites of GST-p53 identified by mass spectrometry analysis. F, GST-p53 wild-type and 3A mutant proteins were analyzed in a kinase assay as in B. G, plasmids encoding wild-type or 3A mutant (CMV)-FLAG-p53 were transiently transfected into H1299 cells, with or without Myc-Aurora B (AurB) expression vector. 20 h post-transfection, cells were lysed and subjected to immunoprecipitation (IP) with p53 antibody (fl-393). Precipitates were immunoblotted with antibodies to p53 (DO-1), Thr(P) and Ser(P), as indicated. Vec, vector. |
Solubility (25C) |
DMSO 102 mg/mL, Water <1 mg/mL, Ethanol 3 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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