AT-9283
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.
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.
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.
| Chemical | |
|---|---|
| CAS Num | 896466-76-5 |
| Chemical Formula | C19H23N7O2 |
| Molecular Weight | 381.43 |
| IUPAC Chemical Name | 1-cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea |
| Exact Mass | 381.19132 |
| Elemental Analysis | C, 59.83; H, 6.08; N, 25.70; O, 8.39 |
| Synonym | AT9283; AT 9283; AT-9283. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C(NC1=CNN=C1C2=NC3=CC(CN4CCOCC4)=CC=C3N2)NC5CC5 |
| Biological | |
| Targets and Effects | Multikinase inhibitor |
| Pathways | Apoptosis |
| Physical | |
| 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). |
| Shelf Life | >5 years if stored properly |
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