AT9283-DataSheet-生命科學(xué)試劑-MedChemExpress

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

2、C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (262.17 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請

3、根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.55 mM); Clear solution2. 請依序添加每種溶劑： 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 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.55 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AT9283種多靶點激酶抑制劑，有效抑制極光激酶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)體外研究 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.體內(nèi)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 您邊的抑制劑師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.