Barasertib (AZD-1152)
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 200420

CAS#: 722543-31-9

Description: Barasertib is an orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152–hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) with potential antineoplastic activity. Upon administration and rapid conversion from the prodrug form in plasma, barasertib specifically binds to and inhibits Aurora kinase B, which results in the disruption of spindle checkpoint functions and chromosome alignment and, so, the disruption of chromosome segregation and cytokinesis. Consequently, cell division and cell proliferation are inhibited and apoptosis is induced in Aurora kinase B-overexpressing tumor cells. IMPORTANT NOTE: AZD-1152HQPA IS NOT AZD-1152 or Barasertib. Many vendors is selling Barasertib with wrong structure


Price and Availability

Size
Price

10mg
USD 265
Size
Price

50mg
USD 850
Size
Price

Barasertib (AZD1152), purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200420
Name: Barasertib (AZD-1152)
CAS#: 722543-31-9
Chemical Formula: C26H31FN7O6P
Exact Mass: 587.20575
Molecular Weight: 587.54
Elemental Analysis: C, 53.15; H, 5.32; F, 3.23; N, 16.69; O, 16.34; P, 5.2 7


Synonym: AZD1152; AZD-1152; AZD 1152; Barasertib.

IUPAC/Chemical Name: 2-(ethyl(3-(4-(5-(2-(3-fluorophenylamino)-2-oxoethyl)-1H-pyrazol-3-ylamino)quinazolin-7-yloxy)propyl)amino)ethyl dihydrogen phosphate

InChi Key: GBJVVSCPOBPEIT-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H31FN7O6P/c1-2-34(10-12-40-41(36,37)38)9-4-11-39-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(35)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17H,2,4,9-12,15H2,1H3,(H,30,35)(H2,36,37,38)(H2,28,29,31,32,33)

SMILES Code: O=P(O)(OCCN(CC)CCCOC1=CC2=NC=NC(NC3=NNC(CC(NC4=CC=CC(F)=C4)=O)=C3)=C2C=C1)O


Technical Data

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).

Harmonized System Code:
293490


Additional Information

722543-50-2 (Barasertib or AZD-1152 dihydrochloride salt)
722543-31-9 (Barasertib or AZD-1152 free form)
722544-51-6 (AZD-1152-HQPA)

Phase I study of  barasertib (AZD1152) .  barasertib (AZD1152) is a highly potent and selective Aurora B kinase inhibitor. The safety, efficacy and pharmacokinetic (PK) profile of barasertib were investigated in Japanese patients with advanced acute myeloid leukemia. Barasertib (50-1200mg) was administered as a continuous 7-day intravenous infusion every 21 days. No dose-limiting toxicities were reported and barasertib 1200mg was chosen for further evaluation in Japanese patients. Neutropenia and febrile neutropenia were the most commonly reported adverse events. The PK profile was similar to Western patients. A promising overall hematologic response rate of 19% was achieved, which warrants further investigation in these patients. (source: Leuk Res. 2011 Oct;35(10):1384-9. ).
 .


References

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.