WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200421
Description: AZD-1152 HQPA, also known as AZD-2811, is a potent and selective Aurora B inhibitor (IC50 of 0.37 nM versus 1368 nM for Aurora B and A kinases, respectively), serine/ threonine kinase inhibitor, and an active metabolite of Barasertib ( AZD-1152). Barasertib is a prodrug and will be converted rapidly to the active drug AZD1152-HQPA in human plasma. Preliminary studies showed that AZD-1152 was active against a variety of solid tumors including colon, breast, and lung cancers. IMPORTANT NOTE: AZD-1152HQPA IS NOT AZD-1152 or Barasertib. Many vendors is selling Barasertib with wrong structure
MedKoo Cat#: 200421
Chemical Formula: C26H30FN7O3
Exact Mass: 507.23942
Molecular Weight: 507.56
Elemental Analysis: C, 61.53; H, 5.96; F, 3.74; N, 19.32; O, 9.46
Synonym: AZD-2811; AZD 2811; AZD2811; AZD-1152HQPA; AZD 1152HQPA; AZD1152HQPA; AZD1152 HQPA; AZD1152-HQPA; AZD1152HQPA; Defosbarasertib
IUPAC/Chemical Name: 2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide
InChi Key: QYZOGCMHVIGURT-UHFFFAOYSA-N
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)
SMILES Code: O=C(NC1=CC=CC(F)=C1)CC2=CC(NC3=C4C=CC(OCCCN(CC)CCO)=CC4=NC=N3)=NN2
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Barasertib-HQPA (AZD2811) is a highly selective Aurora B inhibitor with an IC50 of 0.37 nM in a cell-free assay.|
|In vitro activity:||The restrictive potentials of AZD1152-HQPA on cell viability, colony formation, nucleus morphology, polyploidy, and cell-cycle distribution were investigated. The expressions level of 88 cancer-related miRNAs in untreated and AZD1152-HQPA-treated NB cell line (SK-N-MC) by real-time PCR using miRNA cancer-array system were studied. After normalizing, the fold change of miRNAs was calculated in the AZD1152-HQPA-treated cell as compared to untreated. The results demonstrate that the inhibition of AURKB by AZD1152-HQPA induced potent antitumor activity, suppressed cell survival, and triggered apoptosis and polyploidy in NB cells. AZD1152-HQPA, at a relevant concentration, modulated a substantial number of cancer-related miRNAs in NB cell. Interestingly, by screening the literature, among the 7 top AZD1152-HQPA-induced upregulated miRNAs (> 3-fold change; P < 0.01), all were potential tumor suppressors associated with cell apoptosis and cycle arrest, as well as inhibition of angiogenesis, invasion, and metastasis, while two downregulated miRNAs were known to have oncogenic function. Taken together, this study showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. Reference: J Mol Neurosci. 2018 Aug;65(4):444-455. https://dx.doi.org/10.1007/s12031-018-1118-y|
|In vivo activity:||The effects of this drug on flank and intracranial GBM xenografts was investigated. Daily subcutaneous administration of AZD1152-HQPA was well tolerated. No deaths occurred in the drug or vehicle treated animals during the observation period for flank xenografts or during drug administration in animals bearing intracranial xenografts. Animals that received a 4-day course of 25 or 50 mg/kg/day AZD1152-HQPA had a 71 and 70% reduction in flank xenograft tumor volume respectively when compared to vehicle treated animals at 30 days after tumor inoculation (Fig. 4a–e). Tumor weight 12 days after last dose of AZD1152-HQPA was reduced by 73% in animals treated with 25 or 50 mg/kg/day inhibitor dose (Fig. 4b). The growth inhibiting effect of AZD1152-HQPA was maintained for 7 days. Immunodetection of cleaved Caspase-3, showed a nearly 3-fold increase in apoptotic tumor cells in flank xenografts 1 day after completion of AZD1152-HQPA administration (Fig. 5a) and a 7-fold increase in apoptotic tumor cells was observed in intracranial xenografts (Fig 5b). There was a trend towards decreased Aurora B expression in flank tumors treated with AZD1152-HQPA, but this was not statistically significant 1 day after cessation of drug treatment (P = 0.419). A significant reduction in Histone H3 phosphorylation (P = 0.027) and a trend towards reduced Aurora B threonine 232 phosphorylation (P = 0.108) was observed 1 day after cessation of in vivo AZD1152-HQPA treatment (Online Resource 4). Reference: J Neurooncol. 2012 Jul;108(3):349-60. https://doi.org/10.1007/s11060-012-0835-2|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 507.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Zekri A, Mesbahi Y, Boustanipour E, Sadr Z, Ghaffari SH. The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA). J Mol Neurosci. 2018 Aug;65(4):444-455. doi: 10.1007/s12031-018-1118-y. Epub 2018 Jul 26. PMID: 30051358. 2. Zekri A, Ghaffari SH, Ghanizadeh-Vesali S, Yaghmaie M, Salmaninejad A, Alimoghaddam K, Modarressi MH, Ghavamzadeh A. 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. doi: 10.1007/s13277-014-2664-8. Epub 2014 Oct 3. PMID: 25277659.|
|In vivo protocol:||1. Diaz RJ, Golbourn B, Shekarforoush M, Smith CA, Rutka JT. Aurora kinase B/C inhibition impairs malignant glioma growth in vivo. J Neurooncol. 2012 Jul;108(3):349-60. doi: 10.1007/s11060-012-0835-2. Epub 2012 Mar 1. PMID: 22382783.|
1: Helfrich BA, Kim J, Gao D, Chan DC, Zhang Z, Tan AC, Bunn PA. Barasertib,(AZD1152)a small molecule Aurora B inhibitor, inhibits the growth of SCLC cell lines in vitro and in vivo. Mol Cancer Ther. 2016 Aug 5. pii: molcanther.0298.2016. [Epub ahead of print] PubMed PMID: 27496133.
2: Bushby N, Bergin J, Harding J. [(14) C]-AZD1152 drug substance manufacture: challenges of an IV-infusion dosed human mass balance study in patients. J Labelled Comp Radiopharm. 2016 May 30;59(6):250-4. doi: 10.1002/jlcr.3376. PubMed PMID: 27169761.
3: Ghanizadeh-Vesali S, Zekri A, Zaker F, Zaghal A, Yousefi M, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH. Significance of AZD1152 as a potential treatment against Aurora B overexpression in acute promyelocytic leukemia. Ann Hematol. 2016 Jun;95(7):1031-42. doi: 10.1007/s00277-016-2670-6. Epub 2016 Apr 19. PubMed PMID: 27091351.
4: Zekri A, Ghaffari SH, Yaghmaie M, Estiar MA, Alimoghaddam K, Modarressi MH, Ghavamzadeh A. Inhibitor of Aurora Kinase B Induces Differentially Cell Death and Polyploidy via DNA Damage Response Pathways in Neurological Malignancy: Shedding New Light on the Challenge of Resistance to AZD1152-HQPA. Mol Neurobiol. 2016 Apr;53(3):1808-23. doi: 10.1007/s12035-015-9139-9. Epub 2015 Mar 11. PubMed PMID: 25752998.
5: Collins GP, Eyre TA, Linton KM, Radford J, Vallance GD, Soilleux E, Hatton C. A phase II trial of AZD1152 in relapsed/refractory diffuse large B-cell lymphoma. Br J Haematol. 2015 Sep;170(6):886-90. doi: 10.1111/bjh.13333. Epub 2015 Feb 26. PubMed PMID: 25721307.
6: Zekri A, Ghaffari SH, Ghanizadeh-Vesali S, Yaghmaie M, Salmaninejad A, Alimoghaddam K, Modarressi MH, Ghavamzadeh A. 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. doi: 10.1007/s13277-014-2664-8. Epub 2014 Oct 3. PubMed PMID: 25277659.
7: Kantarjian HM, Sekeres MA, Ribrag V, Rousselot P, Garcia-Manero G, Jabbour EJ, Owen K, Stockman PK, Oliver SD. Phase I study assessing the safety and tolerability of barasertib (AZD1152) with low-dose cytosine arabinoside in elderly patients with AML. Clin Lymphoma Myeloma Leuk. 2013 Oct;13(5):559-67. doi: 10.1016/j.clml.2013.03.019. Epub 2013 Jun 10. PubMed PMID: 23763917; PubMed Central PMCID: PMC3775947.
8: Kantarjian HM, Martinelli G, Jabbour EJ, Quintás-Cardama A, Ando K, Bay JO, Wei A, Gröpper S, Papayannidis C, Owen K, Pike L, Schmitt N, Stockman PK, Giagounidis A; SPARK-AML1 Investigators. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013 Jul 15;119(14):2611-9. doi: 10.1002/cncr.28113. Epub 2013 Apr 19. PubMed PMID: 23605952; PubMed Central PMCID: PMC4132839.
9: Ma YX, Li XZ. [Effect of aurora kinase B inhibitor AZD1152 in the treatment of cisplatin-resistant ovarian carcinoma]. Zhonghua Fu Chan Ke Za Zhi. 2013 Jan;48(1):46-50. Chinese. PubMed PMID: 23531251.
10: Ma Y, Weimer J, Fredrik R, Adam-Klages S, Sebens S, Caliebe A, Hilpert F, Eckmann-Scholz C, Arnold N, Schem C. Aurora kinase inhibitor AZD1152 has an additional effect of platinum on a sequential application at the human ovarian cancer cell line SKOV3. Arch Gynecol Obstet. 2013 Jul;288(1):173-82. doi: 10.1007/s00404-013-2719-x. Epub 2013 Feb 7. PubMed PMID: 23389245.
11: Dennis M, Davies M, Oliver S, D'Souza R, Pike L, Stockman P. 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 Sep;70(3):461-9. doi: 10.1007/s00280-012-1939-2. Epub 2012 Aug 4. PubMed PMID: 22864876; PubMed Central PMCID: PMC3428523.
12: Schwartz GK, Carvajal RD, Midgley R, Rodig SJ, Stockman PK, Ataman O, Wilson D, Das S, Shapiro GI. 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. PubMed PMID: 22661287.
13: Löwenberg B, Muus P, Ossenkoppele G, Rousselot P, Cahn JY, Ifrah N, Martinelli G, Amadori S, Berman E, Sonneveld P, Jongen-Lavrencic M, Rigaudeau S, Stockman P, Goudie A, Faderl S, Jabbour E, Kantarjian H. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6030-6. doi: 10.1182/blood-2011-07-366930. Epub 2011 Oct 5. PubMed PMID: 21976672; PubMed Central PMCID: PMC4186639.
14: Keizer RJ, Zandvliet AS, Beijnen JH, Schellens JH, Huitema AD. Two-stage model-based design of cancer phase I dose escalation trials: evaluation using the phase I program of barasertib (AZD1152). Invest New Drugs. 2012 Aug;30(4):1519-30. doi: 10.1007/s10637-011-9694-5. Epub 2011 May 28. PubMed PMID: 21626115; PubMed Central PMCID: PMC3388254.
15: Tsuboi K, Yokozawa T, Sakura T, Watanabe T, Fujisawa S, Yamauchi T, Uike N, Ando K, Kihara R, Tobinai K, Asou H, Hotta T, Miyawaki S. A Phase I study to assess the safety, pharmacokinetics and efficacy of barasertib (AZD1152), an Aurora B kinase inhibitor, in Japanese patients with advanced acute myeloid leukemia. Leuk Res. 2011 Oct;35(10):1384-9. doi: 10.1016/j.leukres.2011.04.008. Epub 2011 May 11. PubMed PMID: 21565405.
16: Mori N, Ishikawa C, Senba M, Kimura M, Okano Y. Effects of AZD1152, a selective Aurora B kinase inhibitor, on Burkitt's and Hodgkin's lymphomas. Biochem Pharmacol. 2011 May 1;81(9):1106-15. doi: 10.1016/j.bcp.2011.02.010. Epub 2011 Mar 1. Erratum in: Biochem Pharmacol. 2011 Nov 1;82(9):1252. PubMed PMID: 21371446.
17: Azzariti A, Bocci G, Porcelli L, Fioravanti A, Sini P, Simone GM, Quatrale AE, Chiarappa P, Mangia A, Sebastian S, Del Bufalo D, Del Tacca M, Paradiso A. Aurora B kinase inhibitor AZD1152: determinants of action and ability to enhance chemotherapeutics effectiveness in pancreatic and colon cancer. Br J Cancer. 2011 Mar 1;104(5):769-80. doi: 10.1038/bjc.2011.21. Epub 2011 Feb 8. PubMed PMID: 21304529; PubMed Central PMCID: PMC3048212.
18: Moroz MA, Kochetkov T, Cai S, Wu J, Shamis M, Nair J, de Stanchina E, Serganova I, Schwartz GK, Banerjee D, Bertino JR, Blasberg RG. Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging. Clin Cancer Res. 2011 Mar 1;17(5):1099-110. doi: 10.1158/1078-0432.CCR-10-1430. Epub 2011 Jan 18. PubMed PMID: 21245090; PubMed Central PMCID: PMC3079195.
19: Niermann KJ, Moretti L, Giacalone NJ, Sun Y, Schleicher SM, Kopsombut P, Mitchell LR, Kim KW, Lu B. Enhanced radiosensitivity of androgen-resistant prostate cancer: AZD1152-mediated Aurora kinase B inhibition. Radiat Res. 2011 Apr;175(4):444-51. doi: 10.1667/RR2317.1. Epub 2011 Jan 11. PubMed PMID: 21222513; PubMed Central PMCID: PMC3133747.
20: Libertini S, Abagnale A, Passaro C, Botta G, Barbato S, Chieffi P, Portella G. AZD1152 negatively affects the growth of anaplastic thyroid carcinoma cells and enhances the effects of oncolytic virus dl922-947. Endocr Relat Cancer. 2011 Jan 13;18(1):129-41. doi: 10.1677/ERC-10-0234. Print 2011 Feb. PubMed PMID: 21071467.
722543-50-2 (Barasertib or AZD-1152 dihydrochloride salt)
722543-31-9 (Barasertib or AZD-1152 free form)
AZD1152-HQPA is a highly potent and selective Aurora B inhibitor with a Ki of 0.36 nM. AZD1152-HQPA inhibits Aurora A with a Ki of 1.37 nM. AZD1152 is converted rapidly to the active AZD1152-HQPA (Barasertib) in plasma. AZD1152-HQPA has a high specificity versus a panel of 50 other kinases. Consistent with inhibition of Aurora B kinase, addition of AZD1152-HQPA to tumor cells in vitro induces chromosome misalignment, prevents cell division, and consequently reduces cell viability and induces apoptosis.