XL228 is a multi-targeted tyrosine kinase inhibitor with IC₅₀s of 5, 3.1, 1.6, 6.1, 2 nM for Bcr-Abl, Aurora A, IGF-1R, Src and Lyn, respectively.

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 inhibitors including XL228 is profiled against a series of cancer cell lines with known alterations in major signaling pathways. Approximately 30% of the lines demonstrate XL228 IC₅₀ values of <100nm in viability assays, including many lines with characterized alk or fgfr mutations amplifications. xl228 eliminates the phosphorylation of aurora a and b at concentrations above 10 nm. short-term treatment hela cells leads to disruption mitotic spindle formation, majority exhibiting unipolar disorganized chromosomes^[2]. It displays low nanomolar biochemical activity against wild type Abl kinase (K_i=5 nM), as well as the T315I form of Abl resistant to imatinib and dasatinib (K_i=1.4 nM). XL228 inhibits phosphorylation of BCR-ABL and its substrate STAT5 in K562 cells in vitro with IC₅₀s of 33 and 43 nM, respectively^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Single-dose pharmacodynamics studies demonstrate a potent effect of XL228 on BCR-ABL signaling in K562 xenograft tumors. Phosphorylation of BCR-ABL is decreased by 50% at XL228 plasma concentrations of 3.5 μM; a similar decrease in phospho-STAT5 occurred at 0.8 μM plasma concentration^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

437.54

C₂₂H₃₁N₉O

898280-07-4

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 83.33 mg/mL (190.45 mM)

* “≥” means soluble, but saturation unknown.

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• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.75 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.75 mM，饱和度未知) 的澄清溶液。

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• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.75 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.75 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

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• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (4.75 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.75 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Cortes J, et al. Preliminary Clinical Activity in a Phase I Trial of the BCR-ABL/IGF- 1R/Aurora Kinase Inhibitor XL228 in Patients with Ph++ Leukemias with Either Failure to Multiple TKI Therapies or with T315I Mutation. Blood 2008 112:3232

  [2]. Douglas O, et al. Abstract C192: Characterization of the target profile of XL228, a multi‐targeted protein kinase inhibitor in phase 1 clinical development. 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 2007 110:474;