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Barasertib (AZD1152-HQPA)
Aurora Kinase B inhibitor, Potent and selective

Barasertib (AZD1152-HQPA)

Catalog No. A4112
Size Price Stock Qty
10mM (in 1mL DMSO) $100.00 In stock
Evaluation Sample $28.00 In stock
5mg $85.00 In stock
10mg $145.00 In stock
50mg $470.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

Barasertib (AZD1152-HQPA)

Related Biological Data

Barasertib (AZD1152-HQPA)

Related Biological Data

Barasertib (AZD1152-HQPA)

Biological Activity

Description Barasertib (AZD1152-HQPA) is a highly selective inhibitor of Aurora B with IC50 of 0.37 nM, ~100 fold more selective for Aurora B over Aurora A.
Targets Aurora B          
IC50 0.37 nM          

Protocol

Cell experiment: [1]

Cell lines

HL-60 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

25 nM, 72 hours

Applications

The cells exhibited increased DNA contents of 4N and 8N, indicative of polyploidy, within 24–48 h of treatment. After 48–72 h, barasertib-HQPA induced apoptotic cell death, as detected by an increased sub-G1 population compared for that of untreated cells. The induction of polyploidy was obvious at 24–48 h, and thereafter, the nuclei showed morphology typical of apoptosis, such as nuclear fragmentation and condensation. These observations were in accordance with the findings of the flow cytometric analysis.

Animal experiment: [2]

Animal models

Female nude mice injected with SW620, Colo205 or HCT116 cells

Dosage form

Subcutaneous injection, 150 mg/kg/day, minipump infusion over 48 h

Applications

In SW620, HCT116 and Colo205 xenografts significant tumor growth inhibitions of 79% (P<0.001, day 23), 60% (P<0.001, day 25) and 81% (P<0.05, day 21) were observed, respectively. Colo205 xenografts appeared the most sensitive to treatment with a mean tumor volume (± SEM) on day 21 after cell implantation, of 0.42±0.19 cm3 for the barasertib group compared to 2.24±0.75 cm3 (P<0.05) for the vehicle control animals.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Yamauchi T, Uzui K, Shigemi H, et al. Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells. Cancer science, 2013, 104(7): 926-933.

[2] Alferez D G, Goodlad R A, Odedra R, et al. Inhibition of Aurora-B kinase activity confers antitumor efficacy in preclinical mouse models of early and advanced gastrointestinal neoplasia. International journal of oncology, 2012, 41(4): 1475-1485.

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Chemical Properties

Cas No. 722544-51-6 SDF Download SDF
Synonyms AZD1152,INH 34
Chemical Name 2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide
Canonical SMILES CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCO
Formula C26H30FN7O3 M.Wt 507.56
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips No
Shipping Condition No

Research Update

3. Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells. Cancer Sci. 2013 Jul;104(7):926-33. doi: 10.1111/cas.12164. Epub 2013 May 12.
Abstract
As an active metabolite of Barasertib, barasertib-HQPA is an inhibitor of aurora B that potently inhibited growth of HL cells by inducing polyploidy and apoptosis. In order to provide a greater-than-additive cyctotoxicity to HL cells, barasertib-HQPA must be applied before or concurrently with ara-C.
4. Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA. Invest New Drugs. 2013 Oct;31(5):1125-35. doi: 10.1007/s10637-013-9923-1. Epub 2013 Jan 13.
Abstract
Both barasertib and barasertib-hQPA could be efficiently transported by BCRP and MDR1, in which significant barasertib resistance has been observed. MRP2 neither transported barasertibe nor affected its cytotoxicity.
5. Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. Invest New Drugs. 2013 Apr;31(2):370-80. doi: 10.1007/s10637-012-9825-7. Epub 2012 Jun 2.
Abstract
Barasertib, an Aurora B Kinase inhibitor, was generally well tolerated in patients with advanced solid malignancies with MTDs of 150 mg and 220 mg for 48-h continuous infusion and two 2-h infusion respectively, which caused neutropenia as the DLT and mild to modest adverse side effects of hematologic or gastrointestinal etiology.

Background

Barasertib, previously known as AZD1152-hydroxyquinazoline pyrazol anilide (HQPA), is a potent aurora kinase inhibitor, which is resulted from rapid phosphatase-mediated cleavage of the precursor, AZD1152, in serum following parenteral administration in vivo. It shows inhibitory effects against a broad range of aurora kinases, including aurora A kinase (AKB), aurora B kinase (ABK), and aurora C kinase (ACK) with inhibition constant (Ki) of 1369 nM, 0.36 nM, and 17.0 nM respectively, as well as the FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation. Barasertib has demonstrated anti-tumor activity against a range tumor cell lines including those of leukaemic acute myeloid leukemia (AML) origin.

Reference

Martin Grundy, Claire Seedhouse, Nigel H Russell and Monica Pallis. P-glycoprotein and breast cancer resistance protein in acyte myeloid leukaemia cells treated with the aurora-B kinase inhibitor barasertib-Hqpa. BMC Cancer 2011, 11:254

Mike Dennis, Michelle Davies, Stuart Oliver, Roy D’Souza, Laura Pike, and Paul Stockman. Phase I study of the aurora B kinase inhibitor barasertib (AZD1152) to assess the pharmacokinetics, metabolism and excretion in patients with acute myeloid leukemia. Cancer Chemother Pharmacol (2012) 70:461-469