Alpelisib (BYL-719) 是有效，选择性的，具有口服活性的PI3Kα抑制剂。Alpelisib (BYL-719) 对 PIK3CA 突变癌具有靶向性。Alpelisib (BYL-719) 抑制 p110α、p110γ、p110δ、p110β 的IC50分别为 5 nM，250 nM，290 nM，1200 nM。具有抗肿瘤活性。
| 生物活性 | Alpelisib (BYL-719) is a potent, selective, and orally activePI3Kαinhibitor. Alpelisib (BYL-719) shows efficacy in targeting PIK3CA-mutatedcancer. Alpelisib (BYL-719) also inhibits p110α/p110γ/p110δ/p110β with IC50s of 5/250/290/1200 nM, respectively. Antineoplastic activity[1][2][3]. |
| IC50& Target[1][2] | p110α 5 nM (IC50) | p110β 1200 nM (IC50) | p110δ 290 nM (IC50) | p110γ 250 nM (IC50) | p110α-H1047R 4 nM (IC50) | p110α-E545K 4 nM (IC50) |
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体外研究
(In Vitro) | Alpelisib (BYL-719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC50s~4 nM). Alpelisib potently inhibits Akt phosphorylation in cells transformed with PI3Kα (IC50=74±15 nM) and shows significant reduced inhibitory activity in PI3Kβ or PI3Kδ isoforms transformed cells (≥15-fold compared with PI3Kα)[2].
Alpelisib (BYL-719, 0-50 μM; 72 hours) inhibits the cell growth of osteosarcoma cell lines MG63, HOS, POS-1 and MOS-J in a dose-dependent manner[3].
Alpelisib (BYL-719) significantly alters the distribution of cell cycle phases. Alpelisib (BYL-719, 25 μM; 18 hours) induces a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell lines[3].
Cell Proliferation Assay[3] | Cell Line: | MG63, HOS, POS-1, MOS-J | | Concentration: | 10, 20, 30, 40, 50 μM | | Incubation Time: | 72 hours | | Result: | Inhibited the cell growth of all osteosarcoma cell lines tested in a dose-dependent manner with IC50s of 6-15 μM and with IC90s of 24-42 μM. |
Cell Cycle Analysis[3] | Cell Line: | MG63, HOS, POS-1, MOS-J | | Concentration: | 25 μM | | Incubation Time: | 18 hours | | Result: | Induced a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell . |
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体内研究
(In Vivo) | Alpelisib (BYL-719) (12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice; oral administration; daily) significantly reduces tumor volumes and deposition of ectopic bone matrix[3].
Alpelisib has moderate terminal elimination half-life (t1/2=2.9±0.2 h) for rat (1 mg/kg, iv)[1].
| Animal Model: | A 5-week-old female Rj:NMRI-nude mice with human HOS-MNNG osteosarcoma cells; A 5-week-old male C57Bl/6J mice with mouse MOS-J osteosarcoma cells[3] | | Dosage: | 12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice | | Administration: | Oral administration; daily; 22 or 29 days for C57Bl/6J mice or Rj:NMRI-nude mice | | Result: | Significantly reduced tumor volumes and simultaneously reduced tumor growth. |
| Animal Model: | Female Sprague Dawley rats[1] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | I.V. | | Result: | t1/2=2.9±0.2 hours. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 83.33 mg/mL(188.76 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2652 mL | 11.3258 mL | 22.6516 mL | | 5 mM | 0.4530 mL | 2.2652 mL | 4.5303 mL | | 10 mM | 0.2265 mL | 1.1326 mL | 2.2652 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 0.5% MC 0.5%Tween-80 Solubility: 10 mg/mL (22.65 mM); Suspension solution; Need ultrasonic 2. 请依序添加每种溶剂： 1% CMC 0.5%Tween-80 Solubility: 10 mg/mL (22.65 mM); Suspension solution; Need ultrasonic 3. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 5 mg/mL (11.33 mM); Clear solution 4. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.08 mg/mL (4.71 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (4.71 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 5. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.71 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 6. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.71 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。 *以上所有助溶剂都可在本网站选购。
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