XL228 - Aurora Kinase 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEXL228Cat. No.: HY-15749CAS No.: 898280-07-4分式: CHNO分量: 437.54作靶点: Aurora Kinase; Bcr-Abl; IGF-1R; Src作通路: Cell Cycle/DNA Damage; Epigenetics; Protein TyrosineKinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-2

2、0C 1 month溶解性数据体外实验 DMSO : 83.33 mg/mL (190.45 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2855 mL 11.4275 mL 22.8551 mL5 mM 0.4571 mL 2.2855 mL 4.5710 mL10 mM 0.2286 mL 1.1428 mL 2.2855 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。体内实验请根据您的实验动物和给

3、药式选择适当的溶解案，配制前请先配制澄清的储备液，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；澄清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: 2.08 mg/mL (4.75 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.75 mM); C

4、lear solution1/2 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: 2.08 mg/mL (4.75 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 XL228是多靶点的酪氨酸激酶抑制剂，对Bcr-Abl，Aurora A，IGF-1R，Src 和 Lyn 的IC50 值分别为5，3.1，1.6，6.1，2 nM。IC50 & Target Aurora A IGF-1R3.1 nM (IC50) 1.6 nM

5、 (IC50)体外研究 XL228 shows a broad pattern of protein kinase inhibition, including the tyrosine kinases IGF1R, SRC, ABL,FGFR1-3, and ALK and the serine/threonine kinases Aurora A and Aurora B. A panel of kinase inhibitorsincluding XL228 is profiled against a series of cancer cell lines with known alter

6、ations in major signalingpathways. Approximately 30% of the lines demonstrate XL228 IC50 values of 2. It displays low nanomolarbiochemical activity against wild type Abl kinase (Ki=5 nM), as well as the T315I form of Abl resistant toimatinib and dasatinib (Ki=1.4 nM). XL228 inhibits phosphorylation

7、of BCR-ABL and its substrate STAT5 inK562 cells in vitro with IC50s of 33 and 43 nM, respectively 3.体内研究 Single-dose pharmacodynamics studies demonstrate a potent effect of XL228 on BCR-ABL signaling in K562xenograft tumors. Phosphorylation of BCR-ABL is decreased by 50% at XL228 plasma concentratio

8、ns of 3.5M; a similar decrease in phospho-STAT5 occurred at 0.8 M plasma concentration 3.户使本产品发表的科研献 Science. 2017 Dec 1;358(6367). Nat Biomed Eng. 2018;2:578-588. Technical University of Munich. 24.01.2018.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Cortes J, et al. Prelim

9、inary Clinical Activity in a Phase I Trial of the BCR-ABL/IGF- 1R/Aurora Kinase Inhibitor XL228 in Patients withPh+ Leukemias with Either Failure to Multiple TKI Therapies or with T315I Mutation. Blood 2008 112:32322. Douglas O, et al. Abstract C192: Characterization of the target profile of XL228,

10、a multitargeted protein kinase inhibitor in phase 1 clinicaldevelopm ent. Mol Cancer Ther 2009;8(12 Suppl):C192.3. Shah N, et al. Targeting Drug-Resistant CML and Ph+-ALL with the Spectrum Selective Protein Kinase Inhibitor XL228. Blood 2007110:474;McePdfHeightCaution: Product has not been fully valida