Barasertib (AZD1152-HQPA)
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
- 1. Tomoaki Sobajima, Katarzyna M Kowalczyk, et al. "PP6 regulation of Aurora A–TPX2 limits NDC80 phosphorylation and mitotic spindle size." J Cell Biol. 2023 May 1;222(5):e202205117. PMID: 36897279
- 2. Naheed Arfin Borah, Swatishree Sradhanjali, et al. "Aurora Kinase B Expression, Its Regulation and Therapeutic Targeting in Human Retinoblastoma." Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):16. PMID:33704359
- 3. Maik Schuler, Lindsay Tomlinson, et al. "Experiments in the EpiDerm 3D Skin In Vitro Model and Minipigs In Vivo Indicate Comparatively Lower In Vivo Skin Sensitivity of Topically Applied Aneugenic Compounds." Toxicol Sci. 2021 Feb 26;180(1):103-121. PMID:33481035
- 4. Christine M Field, James F Pelletier, et al. "Disassembly of actin and keratin networks by Aurora B kinase at the midplane of cleaving Xenopus laevis eggs." bioRxiv. 2019 January 06.
- 5. Shodai Tanaka, Kaori Senda-Murata, et al. "Live cell imaging of anaphase bridge formation and the subsequent cleavage furrow regression induced by the Aurora B kinase inhibitor AZD1152-HQPA." Bioimages. 2017.10.05
- 6. Hanley ML, Yoo TY, et al. "Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin." Mol Biol Cell. 2017 Apr 12. pii: mbc.E16-12-0860. PMID:28404751
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 507.56 |
| Cas No. | 722544-51-6 |
| Formula | C26H30FN7O3 |
| Synonyms | AZD1152-HQPA,AZD-1152HQPA, AZD1152 HPQA,INH 34 |
| Solubility | ≥25.4 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide |
| SDF | Download SDF |
| Canonical SMILES | CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCO |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
HL-60 cells |
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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. |
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Reaction Conditions |
25 nM, 72 hours |
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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] | |
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Animal models |
Female nude mice injected with SW620, Colo205 or HCT116 cells |
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Dosage form |
Subcutaneous injection, 150 mg/kg/day, minipump infusion over 48 h |
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Applications |
In SW620, HCT116 and Colo205 xenografts significant tumor growth inhibitions of 79% (P |
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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. |
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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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| 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 | |||||
Quality Control & MSDS
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