XL388

製品コードS7035 バッチS703501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H22FN3O4S
分子量 455.5 CAS No. 1251156-08-7
Solubility (25°C)* 体外 DMSO 1.25 mg/mL (2.74 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 XL388 is a highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.
in vitro In MCF-7 cells, XL388 blocks mTORC1 phosphorylation of p70S6K (T389)with an IC50 value of 94 nM and blocks mTORC2 phosphorylationof AKT (S473) with an IC50 value of 350 nM. In vitro, XL388 inhibits the viability of solid and hematopoietic tumor cell lines. The proliferation IC50 is 1.37 μM in MCF-7 cell line. XL388 also synergizes with chemotherapeutics in cell-based assays to block cell viability. [1]
in vivo When dosed orally once daily in mice, XL388 shows robust anti-tumor activity in multiple xenograft models including > 100% tumor growth inhibition in the MCF-7 xenograft model. [1] XL388 displays good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. The mean plasma protein binding of XL388 in human, monkey, dog, rat, and mouse plasma is evaluated at 5 μM and is determined to be 86%, 90%, 89%, 85%, and 84%, respectively. Oral administration of XL388 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity. Strong inhibition of both mTORC1 and mTORC2 is achieved 4−8 h following administration orally at 100 mg/kg. Modest inhibition (39−45%) of phosphorylation of the PI3K target AKT (T308) is also observed 4−8 h post dose.[2]

プロトコル(参考用のみ)

キナーゼアッセイ mTOR ELISA Assay
The measurement of mTOR enzyme activity is performed in an ELISA format following the phosphorylation of 4E-BP1 protein. All experiments are performed in the 384-well format. Generally, 0.5 μL of DMSO containing varying concentrations of the test compound is mixed with 15 μL of the enzyme solution. Kinase reactions are initiated with the addition of 15 μL of a solution containing the substrate. The assay conditions are as follows: 0.2 nM mTOR, 10 μM ATP, and 50 nM NHis-tagged 4E-BP1 in 20 mM Hepes, pH 7.2, 1 mM DTT, 50 mM NaCl, 10 mM MnCl2, 0.02 mg/mL BSA, 0.01% CHAPS, 50 mM β-glycerophophate. Following an incubation of 120 min at ambient temperature, 20 μL of the reaction mixture is transferred to a Ni-chelate-coated 384-well plate. The binding step of the 4E-BP1 protein proceeded for 60 min, followed by washing four times each with 50 μL of Tris-buffered saline solution (TBS). Anti-phospho-4E-BP1 rabbit immunoglobulin G (IgG; 20 μL, 1:5000) in 5% BSA−TBST (0.2% Tween-20 in TBS) is added, and the reaction mixuture is further incubated for 60 min. Incubation with a secondary horseradish peroxidase (HRP)-tagged anti-IgG is similarly performed after the primary antibody is washed off (four washes of 50 μL). Following the final wash step with TBST, 20 μL of SuperSignal ELISA Femto is added and the luminescence measured using an EnVision plate reader.
動物実験 動物モデル MCF-7 xenograft tumors
投薬量 50, 100 mg/kg once daily
投与方法 Orally

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Activation of autophagy in macrophages by pro-resolving lipid mediators. [ Autophagy, 2015, 11(10):1729-44] PubMed: 26506892

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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