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AT9283
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AT9283图片
包装与价格:
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

产品介绍
AT9283 是一种多靶点激酶抑制剂,对 Aurora A/B、JAK2/3、Abl (T315I) 和 Flt3 具有有效的活性(IC50 范围为 1 至 30 nM)。 AT9283 在体外和体内抑制多个实体瘤的生长和存活。

Cell experiment:

Lymphoma cells are seeded at 8,000 per well in 96-well culture plates and allowed to grow for 24 hr followed by the desired treatment with increasing concentrations of the indicated agents for 4 days. Viable cell densities are determined using a CellTiter 96 Cell Proliferation Assay. The IC50 values are estimated by Calcusyn software.

Animal experiment:

SCID mice are injected with 1×107 Granta-519 MCL cells subcutaneously into the right hind flank. When tumors reached a volume of appr 60-100 mm3, mice are divided randomly (pair-matched) into six test groups with 12 mice per cohort: control group (saline), AT9283 (15 mg/kg IP Q1D, 5 days a week × 3 weeks) group, AT9283 (20 mg/kg IP Q1D, 5 days a week × 3 weeks) group, docetaxel (10 mg/kg IV Q1W × 3 weeks) group, AT9283 (15 mg/kg IP Q1D, 5 days a week × 3 weeks) + docetaxel (10 mg/kg IV Q1W × 3 weeks) group and AT9283 (20 mg/kg IP Q1D, 5 days a week × 3 weeks) + docetaxel (10 mg/kg IV Q1W × 3 weeks) group. The length (L) and width (W) of the subcutaneous tumors are measured by calipers and the tumor volume (TV) is calculated as: TV=(L × W2)/2. Mice are sacrificed at the end of study and overall survival for each cohort is analyzed by Kaplan–Meier method.

产品描述

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 IC50value 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.