Alpelisib (BYL-719) 有效抑制 2 种最常见的 PIK3CA 体细胞突变（H1047R、E545K；IC50~4 nM）。 Alpelisib 有效抑制 PI3Kα 转化细胞中的 Akt 磷酸化 (IC50=74±15 nM)，并且在 PI3Kβ 或 PI3Kδ 同种型转化细胞中表现出显着较低的抑制功效（相对于 PI3Kα ≥15 倍）[2]。 Alpelisib（BYL-719，0-50 μM；72 小时）以剂量依赖性方式抑制骨肉瘤细胞系 MG63、HOS、POS-1 和 MOS-J 的细胞增殖 [3]。 Alpelisib (BYL-719) 极大地影响细胞周期阶段的分布。 Alpelisib（BYL-719，25 μM；18 小时）促进人和鼠骨肉瘤细胞系的细胞周期停滞在 G0/G1 期 [3]。

每天口服一次，Alpelisib (BYL-719) 可显着减少肿瘤体积和异位骨基质沉积（C57Bl/6J 小鼠为 12.5 mg/kg 和 50 mg/kg；雌性 Rj:NMRI 裸鼠为 50 mg/kg）[ 3]。在大鼠中，alpelisib（1 mg/kg，静脉注射）具有中等的终末消除半衰期（t1/2=2.9±0.2 h）[1]。

细胞增殖测定[3]
细胞类型： MG63、HOS、POS-1、MOS-J
测试浓度： 10、20、30、40 ，50 μM
孵育时间：72 小时
实验结果： 在一个剂量中抑制所有测试的骨肉瘤细胞系的细胞生长依赖方式，IC50 为 6-15 µM，IC90 为 24-42 µM。

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细胞周期分析 [3]
细胞类型： MG63、HOS、POS-1、MOS-J
测试浓度： 25 μM
孵育时间：18小时
实验结果：诱导人类和小鼠骨肉瘤细胞的细胞周期停滞在G0/G1 阶段。

Animal/Disease Models: 5weeks old female Rj:NMRI nude mice, human HOS-MNNG osteosarcoma cells; 5weeks old male C57Bl/6J mice, mouse MOS-J osteosarcoma cells [3]
Doses: C57Bl/6J mice 12.5 mg/kg and 50 mg/kg; female Rj: NMRI nude mice 50 mg/kg.
Route of Administration: oral; daily
Experimental Results: tumor volume was Dramatically diminished, and tumor growth was also diminished.

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Animal/Disease Models: Female Sprague Dawley rats [1]
Doses: 1 mg/kg (pharmacokinetic/PK/PK study)
Route of Administration: IV
Experimental Results: T1/2=2.9±0.2 hrs (hrs (hours)).

[1]. Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8.
[2]. Fritsch C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29.
[3]. Gobin B, et al. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96.

C19H23CLF3N5O2S

477.93

1584128-91-5

Alpelisib;1217486-61-7

CC1N=C(NC(N2CCC[C@H]2C(=O)N)=O)SC=1C1=CC=NC(C(C)(C)C(F)(F)F)=C1.Cl

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。