AT9283
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AT9283是用基于片段的药物设计方法合成的小杂环分子。AT9283是一种新型的Aurora激酶抑制剂，有效地抑制Aurora激酶A和B（IC50 = 3 nM）、Janus激酶（JAKS）、Abelson激酶（BCR-ABL T315I）和Flt-3。Aurora激酶属于丝氨酸/苏氨酸激酶家族，可调节有丝分裂和减数分裂。据发现，AT9283对白血病细胞、骨髓增殖性疾病和多种实体瘤细胞系具有疗效。研究结果表明，在侵袭性B细胞NHL细胞系中，AT9283抑制Aurora激酶B，从而具有抗增殖活性以及诱导多倍体和细胞凋亡。
参考文献：
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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 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是有效的Aurora抑制剂，对Aurora A、Aurora B、JAK3、JAK2和c-Abl的IC50值分别为3 nM、3 nM、1.1 nM、1.2 nM和4 nM。 | |||||
| 靶点 | Aurora A | Aurora B | JAK3 | JAK2 | c-Abl | |
| IC50 | 3 nM | 3 nM | 1.1 nM | 1.2 nM | 4 nM | |
质量控制和MSDS
- 批次:
化学结构
相关生物数据
相关生物数据
