AT9283-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAT9283Cat. No.: HY-50514CAS No.: 896466-04-9分式: CHNO分量: 381.43作靶点: JAK; Aurora Kinase; Autophagy作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt; CellCycle/DNA Damage; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80

2、C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (262.17 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6217 mL 13.1086 mL 26.2171 mL5 mM 0.5243 mL 2.6217 mL 5.2434 mL10 mM 0.2622 mL 1.3109 mL 2.6217 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请

3、根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.55 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.55 m

4、M); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.55 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AT9283种多靶点激酶抑制剂，有效抑制极光激酶A/B，JAK2/3 (IC50=1.2 nM, 1.1 nM)。IC50 & Target JAK3 JAK2 Aurora A Aurora B1.1 nM (IC50) 1.2 nM (IC50) 3

5、nM (IC50) 3 nM (IC50)Abl (T315I)4 nM (IC50)体外研究 AT9283 leads to a clear polyploid phenotype by inhibiting the activity of Aurora B kinase in HCT116 cells withIC50 of 30 nM. Furthermore, AT9283 also produces the potent inhibition on HCT116 colony formation 1.AT9283 induces apoptosis in a dose and tim

6、e dependent manner and inhibits cell proliferation with an IC50 1 M in B-NHL cell lines 2. AT9283 inhibits growth, induces dose dependent cytotoxicity, and inhibitsSTAT3 signaling pathway in MM cell lines. T9283 inhibits phospho Histone H3 and phospho Aurora A at Thr288. AT9283 increases G2/M phase

7、and induces apoptosis of MM cells in a time-dependent manner 3.体内研究 In HCT116 human colon carcinoma xenograft bearing mice, AT9283 treatment (15 mg/kg and 20 mg/kg) for16 days results in a significant tumor growth inhibition of 67% and 76%, respectively. In addition, AT9283also exhibits a significan

8、tly longer half-life in tumors (2.5 hours) compared with plasma (0.5 hour) and modestoral bioavailability in mice 1. AT9283 (15 mg/kg) and docetaxel (10 mg/kg) alone has modest anti-tumoractivity. T9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrate astatistically sign

9、ificant tumor growth inhibition and enhance survival inmouse xenograft model of mantle celllymphoma 2. AT9283 (45 mg/kg, i.p.) inhibits tumor growth in mice. Two cycles of AT9283 45 mg/kg 14hours after drug administration confirm decreased expression of phospho-Histone H3 and Aurora B in treatedanim

10、als 3.PROTOCOLCell Assay 2 Lymphoma cells are seeded at 8,000 per well in 96-well culture plates and allowed to grow for 24 hr followedby the desired treatment with increasing concentrations of the indicated agents for 4 days. Viable celldensities are determined using a CellTiter 96 Cell Proliferati

11、on Assay. The IC50 values are estimated byCalcusyn software.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal SCID mice are injected with 1107 Granta-519 MCL cells subcutaneously into the right hind flank. WhenAdministration 2 tumors reached a volu

12、me of appr 60-100 mm3, mice are divided randomly (pair-matched) into six test groupswith 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,2/3 Master of Sm

13、all Molecules 您边的抑制剂师www.MedChemEAT9283 (15 mg/kg IP Q1D, 5 days a week 3 weeks) + docetaxel (10 mg/kg IV Q1W 3 weeks) group andAT9283 (20 mg/kg IP Q1D, 5 days a week 3 weeks) + docetaxel (10 mg/kg IV Q1W 3 weeks) group. Thelength (L) and width (W) of the subcutaneous tumors are measured by calipers

14、 and the tumor volume (TV) iscalculated as: TV=(L W2)/2. Mice are sacrificed at the end of study and overall survival for each cohort isanalyzed by KaplanMeier method.MCE has not independently confirmed the accuracy of these methods. They are for reference only. Sci Transl Med. 2018 Jul 18;10(450).

15、pii: eaaq1093. Patent. US20180263995A1. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Howard S, et al. Fragment-Based Discovery of the Pyrazol-4-yl Urea (AT9283), a Multitargeted Kinase Inhibitor with Potent AuroraKinase Activity. Journal o

16、f 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 Jun15;130(12):2997-3005.3. Santo L, et al. Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition eitheralone or in combination with lenalidomide.