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Purity: ≥98%
Barasertib ( INH34; AZD1152 or AZD1152-HQPA) is a novel, potent, highly selective, orally bioavailable small-molecule Aurora B inhibitor with potential antitumor activity. It inhibits Aurora B with an IC50 of 0.37 nM in a cell-free assay. As a dihydrogen phosphate pro-drug of Barasertib-hQPA, it shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. Barasertib 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.
Targets |
Aurora B (IC50 = 0.37 nM)
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ln Vitro |
In newly isolated leukemia cells, barasertib-HQPA (3 μM, 3 hours) dramatically lowers the expression of phosphorylated variants of histone H3 [1]. In plasma, barasertib-HQPA is quickly transformed into active barasertib-HQPA [2]. In the LNCaP cell line, barasertib-HQPA therapy causes suboptimal cell survival, polyploidy, and cell death [3]. Significant antiproliferative effects caused by barasertib-HQPA are accompanied by polyploid population emergence, which typically results in apoptosis [4].
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ln Vivo |
The development and weight of tumors treated with AZD1152 were considerably decreased by barasertib-HQPA (AZD1152, 25 mg/kg) [1]. In human MOLM13 leukemia xenografts, barasertib-HQPA (AZD1152, 5 mg/kg) amplifies the suppression of proliferation caused by vincristine or daunorubicin [1]. Effectively inhibiting human colon, lung, and hematological tumor xenografts in immunodeficient mice, barasertib-HQPA (AZD1152, 10–150 mg/kg/d) (mean tumor growth inhibition range, 55% to z100%; P < 0.05) [2].
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Cell Assay |
Cell Proliferation Assay[1].
Cell Types: AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells. Tested Concentrations: 0-100 nM. (Barasertib -HQPA) Incubation Duration: 48 h. Experimental Results: IC50 values ranged from 3 nM to 40 nM. |
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Animal Protocol |
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References |
[1]. Yang, Jing., et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood. 2007 Sep 15;110(6):2034-40.
[2]. Wilkinson RW, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007 Jun 15;13(12):3682-8. [3]. Zekri A, et al. AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy. Tumour Biol. 2015 Feb;36(2):623-32. [4]. Oke A, et al. AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo. Cancer Res. 2009 May 15;69(10):4150-8. |
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Additional Infomation |
AZD-1152 is a member of the of quinazolines that is 4-aminoquinazolin-7-ol in which the amino group at position 4 has been substituted by a 5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl group, while the hydroxy group at position 7 has been converted into the corresponding 3-[ethyl(2-hydroxyethyl)aminopropyl ether. It has a role as an antineoplastic agent and an Aurora kinase inhibitor. It is a member of quinazolines, a secondary carboxamide, a tertiary amino compound, a secondary amino compound, a member of pyrazoles, a primary alcohol, a member of monofluorobenzenes and an anilide.
Defosbarasertib is a small-molecule inhibitor of the serine-threonine kinase Aurora B, with potential antineoplastic activity. Upon administration, defosbarasertib specifically binds to and inhibits Aurora kinase B, which disrupts spindle checkpoint functions and chromosome alignment, and results in the disruption of chromosome segregation and cytokinesis. This inhibits cell division and cell proliferation and induces apoptosis in Aurora kinase B-overexpressing tumor cells. Aurora kinase B, a serine/threonine protein kinase that functions in the attachment of the mitotic spindle to the centromere, is overexpressed in a wide variety of cancer cell types. Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation.[1] |
Molecular Formula |
C26H30FN7O3
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Molecular Weight |
507.56
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Exact Mass |
507.23941
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Elemental Analysis |
C, 61.53; H, 5.96; F, 3.74; N, 19.32; O, 9.46
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CAS # |
722544-51-6
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Related CAS # |
Barasertib;722543-31-9 (free acid); 722543-50-2 (2HCl); 957104-91-5; 722544-51-6
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PubChem CID |
16007391
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Appearance |
Typically exists as white to yellow solids at room temperature
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Density |
1.4±0.1 g/cm3
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Boiling Point |
796.7±60.0 °C at 760 mmHg
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Flash Point |
435.6±32.9 °C
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Vapour Pressure |
0.0±2.9 mmHg at 25°C
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Index of Refraction |
1.677
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LogP |
2.82
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tPSA |
128.29
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SMILES |
O=C(NC1=CC=CC(F)=C1)CC2=CC(NC3=C4C=CC(OCCCN(CC)CCO)=CC4=NC=N3)=NN2
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InChi Key |
QYZOGCMHVIGURT-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H30FN7O3/c1-2-34(10-11-35)9-4-12-37-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(36)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17,35H,2,4,9-12,15H2,1H3,(H,30,36)(H2,28,29,31,32,33)
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Chemical Name |
2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide
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Synonyms |
INH-34; INH34; AZD 2811; AZD2811; INH 34; AZD1152-HQPA; AZD1152; AZD-1152; AZD 1152 HQPA; AZD-2811; AZD-1152HQPA; AZD 1152HQPA; AZD1152HQPA; AZD1152 HQPA; AZD1152-HQPA; AZD1152HQPA.AZD1152-HQPA; AZD-1152HQPA; barasertib-hQPA; Barasertib (AZD1152-HQPA); defosbarasertib; INH 34; 2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide;
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% propylene glycol:30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9702 mL | 9.8511 mL | 19.7021 mL | |
5 mM | 0.3940 mL | 1.9702 mL | 3.9404 mL | |
10 mM | 0.1970 mL | 0.9851 mL | 1.9702 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT01019161 | Completed | Drug: AZD1152 Drug: C14 AZD1152 |
Acute Myeloid Leukaemia | AstraZeneca | November 2009 | Phase 1 |
NCT03217838 | Terminated | Drug: AZD2811 Drug: Azacitidine |
Acute Myeloid Leukaemia | AstraZeneca | July 31, 2017 | Phase 1 |
NCT00926731 | Completed | Drug: AZD1152 Drug: LDAC (low dose cytosine arabinoside) |
Acute Myeloid Leukemia | AstraZeneca | June 2009 | Phase 1 |