| CAS NO: | 896466-04-9 |
| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 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 |
| 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 | 为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。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。 |
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.
| Cell experiment:[1] | |
Cell lines | HCT116 cells |
Reaction Conditions | 1 nM ~ 10 μM AT9283 for 72 h incubation |
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] | |
Animal models | Male BALB/c mice injected subcutaneously with HCT116 cells |
Dosage form | 15 and 20 mg/kg Administered intraperitoneally |
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. |
Note | The technical data provided above is for reference only. |
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. | |
| 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 | |
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