AT9283
AT9283, a synthetic small heterocyclic molecule discovered using a fragment-based approach, is a novel inhibitor of aurora kinase, a family of serine/threonine kinases regulating both mitosis and meiosis, that potently inhibits Aurora kinases A and B, with 50% inhibition concentration IC50 value of 3 nM, as well as Janus kinases (JAKs), Abelson kinase (BCRABL T315I) and Flt-3. AT9283 has been found to be therapeutic in leukemic cells, myeloproliferative disorders and multiple solid tumor cell lines. Study results have shown that AT9283 exhibits anti-proliferative activity and induces polyploidy and apoptosis in aggressive B-cell NHL cell lines associated with inhibition of Aurora kinase B.
Reference
Qi W, Liu X, Cooke LS, Persky DO, Miller TP, Squires M, Mahadevan D. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas. Int J Cancer. 2012 Jun 15;130(12):2997-3005. doi: 10.1002/ijc.26324. Epub 2011 Nov 19.
Arkenau HT, Plummer R, Molife LR, Olmos D, Yap TA, Squires M, Lewis S, Lock V, Yule M, Lyons J, Calvert H, Judson I. A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies. Ann Oncol. 2012 May;23(5):1307-13. doi: 10.1093/annonc/mdr451. Epub 2011 Oct 19.
- 1. Laura Torrente, Gunjit Maan, et al. "High NRF2 Levels Correlate with Poor Prognosis in Colorectal Cancer Patients and with Sensitivity to the Kinase Inhibitor AT9283 In Vitro." Biomolecules. 2020 Sep 25;10(10):1365. PMID:32992842
- 2. Laura Torrente, Gunjit Maan, et al. "The kinase inhibitor AT9283 selectively kills colorectal cancer cells with hyperactive NRF2." bioRxiv. 2019, October 21.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 381.43 |
| Cas No. | 896466-04-9 |
| Formula | C19H23N7O2 |
| Solubility | insoluble in H2O; ≥19.05 mg/mL in DMSO; ≥47.6 mg/mL in EtOH with ultrasonic |
| Chemical Name | 1-cyclopropyl-3-[(3Z)-3-[5-(morpholin-4-ylmethyl)benzimidazol-2-ylidene]-1,2-dihydropyrazol-4-yl]urea |
| SDF | Download SDF |
| Canonical SMILES | C1CC1NC(=O)NC2=CNNC2=C3N=C4C=CC(=CC4=N3)CN5CCOCC5 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
HCT116 cells |
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Reaction Conditions |
1 nM ~ 10 μM AT9283 for 72 h incubation |
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Applications |
AT9283 resulted in a clear polyploid phenotype by inhibiting the activity of Aurora B kinase in HCT116 cells, with an IC50 value of 30 nM. Furthermore, AT9283 also demonstrated potent inhibition of HCT116 colony formation, with an IC50 value of 12 nM. |
| Animal experiment:[1] | |
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Animal models |
Male BALB/c mice injected subcutaneously with HCT116 cells |
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Dosage form |
15 and 20 mg/kg Administered intraperitoneally |
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Applications |
In HCT116 human colon carcinoma xenograft bearing mice, AT9283 treatment (15 mg/kg and 20 mg/kg) for 16 days resulted in a significant tumor growth inhibition of 67% and 76%, respectively. These doses were well tolerated with mean body weight being maintained above 90% relative to the starting weight. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Howard S, Berdini V, Boulstridge JA, et al. Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. Journal of Medicinal Chemistry, 2009, 52(2): 379-388. |
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| Description | AT9283 is a potent inhibitor of Aurora with IC50 values of 3 nM, 3 nM, 1.1 nM, 1.2 nM and 4 nM for Aurora A, Aurora B, JAK3, JAK2 and c-Abl, respectively. | |||||
| Targets | Aurora A | Aurora B | JAK3 | JAK2 | c-Abl | |
| IC50 | 3 nM | 3 nM | 1.1 nM | 1.2 nM | 4 nM | |
Quality Control & MSDS
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Chemical structure
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Related Biological Data
