Cenisertib (AS703569)
Cenisertib, also known as AS-703569 or R763; is an orally bioavailable, synthetic, small-molecule multi-Aurora kinase inhibitor with potential antineoplastic activity. Cenisertib selectively binds to and inhibits multiple Aurora kinases (AKs), which may result in the inhibition of cell division and proliferation, and the induction of apoptosis in tumor cells that overexpress AKs. Overexpressed in certain tumor cell types, AKs, a family of serine-threonine kinases, are important regulators of cell division and proliferation that are involved in controlling chromatid segregation.
1: Illert AL, Seitz AK, Rummelt C, Kreutmair S, Engh RA, Goodstal S, Peschel C, Duyster J, von Bubnoff N. Inhibition of Aurora kinase B is important for biologic activity of the dual inhibitors of BCR-ABL and Aurora kinases R763/AS703569 and PHA-739358 in BCR-ABL transformed cells. PLoS One. 2014 Nov 26;9(11):e112318. doi: 10.1371/journal.pone.0112318. eCollection 2014. PubMed PMID: 25426931; PubMed Central PMCID: PMC4245092.
2: Mita M, Gordon M, Rejeb N, Gianella-Borradori A, Jego V, Mita A, Sarantopoulos J, Sankhala K, Mendelson D. A phase l study of three different dosing schedules of the oral aurora kinase inhibitor MSC1992371A in patients with solid tumors. Target Oncol. 2014 Sep;9(3):215-24. doi: 10.1007/s11523-013-0288-3. Epub 2013 Jul 6. PubMed PMID: 23832397.
3: Graux C, Sonet A, Maertens J, Duyster J, Greiner J, Chalandon Y, Martinelli G, Hess D, Heim D, Giles FJ, Kelly KR, Gianella-Borradori A, Longerey B, Asatiani E, Rejeb N, Ottmann OG. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies. Leuk Res. 2013 Sep;37(9):1100-6. doi: 10.1016/j.leukres.2013.04.025. Epub 2013 Jun 5. PubMed PMID: 23746966.
4: Raymond E, Alexandre J, Faivre S, Goldwasser F, Besse-Hammer T, Gianella-Borradori A, Jego V, Trandafir L, Rejeb N, Awada A. A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors. Invest New Drugs. 2014 Feb;32(1):94-103. doi: 10.1007/s10637-013-9950-y. Epub 2013 Mar 29. PubMed PMID: 23539344.
5: Romanelli A, Clark A, Assayag F, Chateau-Joubert S, Poupon MF, Servely JL, Fontaine JJ, Liu X, Spooner E, Goodstal S, de Cremoux P, Bièche I, Decaudin D, Marangoni E. Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence after chemotherapy in patient-derived triple-negative breast cancer xenografts. Mol Cancer Ther. 2012 Dec;11(12):2693-703. doi: 10.1158/1535-7163.MCT-12-0441-T. Epub 2012 Sep 25. PubMed PMID: 23012245.
6: Curtin ML, Heyman HR, Frey RR, Marcotte PA, Glaser KB, Jankowski JR, Magoc TJ, Albert DH, Olson AM, Reuter DR, Bouska JJ, Montgomery DA, Palma JP, Donawho CK, Stewart KD, Tse C, Michaelides MR. Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4750-5. doi: 10.1016/j.bmcl.2012.05.067. Epub 2012 May 26. PubMed PMID: 22695126.
7: Martinelli G, Iacobucci I, Papayannidis C, Soverini S. New targets for Ph+ leukaemia therapy. Best Pract Res Clin Haematol. 2009 Sep;22(3):445-54. doi: 10.1016/j.beha.2009.08.002. Review. PubMed PMID: 19959093.
8: McLaughlin J, Markovtsov V, Li H, Wong S, Gelman M, Zhu Y, Franci C, Lang D, Pali E, Lasaga J, Low C, Zhao F, Chang B, Gururaja TL, Xu W, Baluom M, Sweeny D, Carroll D, Sran A, Thota S, Parmer M, Romane A, Clemens G, Grossbard E, Qu K, Jenkins Y, Kinoshita T, Taylor V, Holland SJ, Argade A, Singh R, Pine P, Payan DG, Hitoshi Y. Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113. doi: 10.1007/s00432-009-0641-1. PubMed PMID: 19609559.
2: Mita M, Gordon M, Rejeb N, Gianella-Borradori A, Jego V, Mita A, Sarantopoulos J, Sankhala K, Mendelson D. A phase l study of three different dosing schedules of the oral aurora kinase inhibitor MSC1992371A in patients with solid tumors. Target Oncol. 2014 Sep;9(3):215-24. doi: 10.1007/s11523-013-0288-3. Epub 2013 Jul 6. PubMed PMID: 23832397.
3: Graux C, Sonet A, Maertens J, Duyster J, Greiner J, Chalandon Y, Martinelli G, Hess D, Heim D, Giles FJ, Kelly KR, Gianella-Borradori A, Longerey B, Asatiani E, Rejeb N, Ottmann OG. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies. Leuk Res. 2013 Sep;37(9):1100-6. doi: 10.1016/j.leukres.2013.04.025. Epub 2013 Jun 5. PubMed PMID: 23746966.
4: Raymond E, Alexandre J, Faivre S, Goldwasser F, Besse-Hammer T, Gianella-Borradori A, Jego V, Trandafir L, Rejeb N, Awada A. A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors. Invest New Drugs. 2014 Feb;32(1):94-103. doi: 10.1007/s10637-013-9950-y. Epub 2013 Mar 29. PubMed PMID: 23539344.
5: Romanelli A, Clark A, Assayag F, Chateau-Joubert S, Poupon MF, Servely JL, Fontaine JJ, Liu X, Spooner E, Goodstal S, de Cremoux P, Bièche I, Decaudin D, Marangoni E. Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence after chemotherapy in patient-derived triple-negative breast cancer xenografts. Mol Cancer Ther. 2012 Dec;11(12):2693-703. doi: 10.1158/1535-7163.MCT-12-0441-T. Epub 2012 Sep 25. PubMed PMID: 23012245.
6: Curtin ML, Heyman HR, Frey RR, Marcotte PA, Glaser KB, Jankowski JR, Magoc TJ, Albert DH, Olson AM, Reuter DR, Bouska JJ, Montgomery DA, Palma JP, Donawho CK, Stewart KD, Tse C, Michaelides MR. Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4750-5. doi: 10.1016/j.bmcl.2012.05.067. Epub 2012 May 26. PubMed PMID: 22695126.
7: Martinelli G, Iacobucci I, Papayannidis C, Soverini S. New targets for Ph+ leukaemia therapy. Best Pract Res Clin Haematol. 2009 Sep;22(3):445-54. doi: 10.1016/j.beha.2009.08.002. Review. PubMed PMID: 19959093.
8: McLaughlin J, Markovtsov V, Li H, Wong S, Gelman M, Zhu Y, Franci C, Lang D, Pali E, Lasaga J, Low C, Zhao F, Chang B, Gururaja TL, Xu W, Baluom M, Sweeny D, Carroll D, Sran A, Thota S, Parmer M, Romane A, Clemens G, Grossbard E, Qu K, Jenkins Y, Kinoshita T, Taylor V, Holland SJ, Argade A, Singh R, Pine P, Payan DG, Hitoshi Y. Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113. doi: 10.1007/s00432-009-0641-1. PubMed PMID: 19609559.
| Chemical | |
|---|---|
| CAS Num | 871357-89-0 |
| Chemical Formula | C24H30FN7O |
| Molecular Weight | 451.54 |
| IUPAC Chemical Name | (1S,2S,3R,4R)-3-((5-fluoro-2-((3-methyl-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxamide |
| Exact Mass | 451.24959 |
| Elemental Analysis | C, 63.84; H, 6.70; F, 4.21; N, 21.71; O, 3.54 |
| Synonym | R763; R 763; R-763; AS703569; AS-703569; AS 703569; UNII5277GPA358; MSC1992371A; Cenisertib. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C([C@H]1[C@](C2)([H])C=C[C@]2([H])[C@H]1NC3=NC(NC4=CC=C(N5CCN(C)CC5)C(C)=C4)=NC=C3F)N |
| Biological | |
| Targets and Effects | Aurora kinase 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 | >2 years if stored properly |
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