>>Signaling Pathways>> Ubiquitination/ Proteasome>> Autophagy>>AT9283

AT9283

Catalog No.GC10638

A broad spectrum kinase inhibitor

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AT9283 Chemical Structure

Cas No.: 896466-04-9

Size 가격 재고 수량
10mM (in 1mL DMSO)
US$71.00
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2mg
US$53.00
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5mg
US$69.00
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10mg
US$115.00
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50mg
US$349.00
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100mg
US$590.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

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.

References:

[1]. Howard S, 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.
[2]. Qi W, et al. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas. Int J Cancer. 2012 Jun 15;130(12):2997-3005.
[3]. Santo L, et al. Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide. Clin Cancer Res. 2011 May 15;17(10):3259-71

Background

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.

Chemical Properties

Cas No. 896466-04-9 SDF
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
Formula C19H23N7O2 M.Wt 381.43
Solubility ≥ 19.05 mg/mL in DMSO, ≥ 47.6 mg/mL in EtOH with ultrasonic Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.6217 mL 13.1086 mL 26.2171 mL
5 mM 0.5243 mL 2.6217 mL 5.2434 mL
10 mM 0.2622 mL 1.3109 mL 2.6217 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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