AT-9283 free base
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MedKoo CAT#: 200322

CAS#: 896466-04-9 (free base)

Description: AT9283 is a multikinase inhibitor, is also a small-molecule inhibitor of several kinases with potential antineoplastic activity. Multikinase inhibitor AT9283 binds to and inhibits Aurora kinases A and B, JAK2 (Janus kinase 2) and the kinase BCR-ABL, which may result in the inhibition of cellular division and proliferation and the induction of apoptosis in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis; JAK2 is a kinase that transduces signals from the single chain and IL-3 cytokine receptor families, and from the IFN-gamma receptors; BCR-ABL is a fusion protein with tyrosine kinase activity that is commonly found in CML.


Chemical Structure

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AT-9283 free base
CAS# 896466-04-9 (free base)

Theoretical Analysis

MedKoo Cat#: 200322
Name: AT-9283 free base
CAS#: 896466-04-9 (free base)
Chemical Formula: C19H23N7O2
Exact Mass: 381.19132
Molecular Weight: 381.43
Elemental Analysis: C, 59.83; H, 6.08; N, 25.70; O, 8.39

Price and Availability

Size Price Availability Quantity
100.0mg USD 850.0 2 Weeks
200.0mg USD 1450.0 2 Weeks
500.0mg USD 2150.0 2 Weeks
1.0g USD 3250.0 2 Weeks
2.0g USD 5450.0 2 Weeks
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Related CAS #: 896466-61-8 (HCl)   896466-04-9 (free base)   896466-76-5 (lactate)    

Synonym: AT9283; AT 9283; AT-9283; AT-9283 free base.

IUPAC/Chemical Name: 1-cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea

InChi Key: LOLPPWBBNUVNQZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H23N7O2/c27-19(21-13-2-3-13)24-16-10-20-25-17(16)18-22-14-4-1-12(9-15(14)23-18)11-26-5-7-28-8-6-26/h1,4,9-10,13H,2-3,5-8,11H2,(H,20,25)(H,22,23)(H2,21,24,27)

SMILES Code: O=C(NC1=CNN=C1C2=NC3=CC(CN4CCOCC4)=CC=C3N2)NC5CC5

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

Preparing Stock Solutions

The following data is based on the product molecular weight 381.43 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.

Recalculate based on batch purity %
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

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1: Podesta JE, Sugar R, Squires M, Linardopoulos S, Pearson AD, Moore AS. Adaptation of the plasma inhibitory activity assay to detect Aurora, ABL and FLT3 kinase inhibition by AT9283 in pediatric leukemia. Leuk Res. 2011 Sep;35(9):1273-5. Epub 2011 Jun 12. PubMed PMID: 21665275.

2: Santo L, Hideshima T, Cirstea D, Bandi M, Nelson EA, Gorgun G, Rodig S, Vallet S, Pozzi S, Patel K, Unitt C, Squires M, Hu Y, Chauhan D, Mahindra A, Munshi NC, Anderson KC, Raje N. Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide. Clin Cancer Res. 2011 May 15;17(10):3259-71. Epub 2011 Mar 23. PubMed PMID: 21430070.

3: Kimura S. AT-9283, a small-molecule multi-targeted kinase inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs. 2010 Dec;11(12):1442-9. Review. PubMed PMID: 21154126.

4: Tanaka R, Squires MS, Kimura S, Yokota A, Nagao R, Yamauchi T, Takeuchi M, Yao H, Reule M, Smyth T, Lyons JF, Thompson NT, Ashihara E, Ottmann OG, Maekawa T. Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells. Blood. 2010 Sep 23;116(12):2089-95. Epub 2010 Jun 14. PubMed PMID: 20548094.

5: Dawson MA, Curry JE, Barber K, Beer PA, Graham B, Lyons JF, Richardson CJ, Scott MA, Smyth T, Squires MS, Thompson NT, Green AR, Wallis NG. AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol. 2010 Jul;150(1):46-57. Epub 2010 May 7. PubMed PMID: 20507304.

6: Lok W, Klein RQ, Saif MW. Aurora kinase inhibitors as anti-cancer therapy. Anticancer Drugs. 2010 Apr;21(4):339-50. Review. PubMed PMID: 20016367.

7: Curry J, Angove H, Fazal L, Lyons J, Reule M, Thompson N, Wallis N. Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283. Cell Cycle. 2009 Jun 15;8(12):1921-9. Epub 2009 Jun 15. PubMed PMID: 19440047.

8: Pinel S, Barbault-Foucher S, Lott-Desroches MC, Astier A. [Inhibitors of aurora kinases]. Ann Pharm Fr. 2009 Mar;67(2):69-77. Epub 2009 Feb 23. Review. French. PubMed PMID: 19298889.

9: Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL, Heathcote M, Maman S, Matthews JE, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Rees DC, Reule M, Tisi D, Williams G, Vinković M, Wyatt PG. Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem. 2009 Jan 22;52(2):379-88. PubMed PMID: 19143567.

10: Bayés M, Rabasseda X. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jan-Feb;30(1):67-99. PubMed PMID: 18389098.



Additional Information

AT9283 has been investigated as monotherapy in patients with advanced solid tumors in two phase 1, open-label, dose-escalation trials at centers in the UK, USA and Canada. The two trials confirmed AT9283 is safe and well tolerated in patients with advanced solid malignancies. Oral bioavailability of AT9283 in humans has also been demonstrated. In conjunction with Cancer Research UK, Astex Pharmaceuticals™ is also investigating the activity of single agent AT9283 in pediatric patients with solid tumors in a trial being conducted at multiple sites in the UK.
 
AT9283 has been investigated in a phase 1/2 open-label, dose-escalation trial to assess the safety, tolerability and preliminary efficacy of AT9283 as monotherapy in patients with acute leukemia. The trial was conducted at centers in the USA. AT9283 is also being investigated in a phase 2 setting in a chemotherapy refractory, multiple myeloma patient population in a trial being sponsored by the NCIC Clinical Trials Group in Canada. An additional pediatric leukemia trial being sponsored by Cancer Research UK is due to begin during 2011. To learn more about the development status of this compound, please see the most recent Astex Pharmaceuticals presentations.  AT9283 is wholly owned by Astex Pharmaceuticals, with a pending license to Montigen Pharmaceuticals, contigent on Montigen financing. (source: http://astx.com).