M2698 (MSC2363318A) 是一种具有口服活性，ATP 竞争的，选择性的p70S6K和Akt双重抑制剂，对于 p70S6K，Akt1 和 Akt3 的IC50均为 1 nM。M2698 可以透过血脑屏障，具有抗癌活性。
| 生物活性 | M2698 (MSC2363318A) is an orally active, ATP competitive, selectivep70S6KandAktdual-inhibitor withIC50s of 1 nM forp70S6K,Akt1andAkt3. M2698 can cross the blood-brain barrier and has anti-cancer activity[1]. |
| IC50& Target[1] | p70S6K 1 nM (IC50) | Akt1 1 nM (IC50) | Akt3 1 nM (IC50) |
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体外研究
(In Vitro) | M2698 (0.3 nM to 50 M; 72 hours) inhibits proliferation in a dose-dependent manner in breast tumors cell lines with IC50s of 0.02-8.5 μM[1].
M2698 (0.3, 1 μM; 24 hours) inhibits p70S6K activity and induces feedback loop phosphorylation on Akt and suppresses Akt activity in breast cancer cell lines[1].
M2698 inhibits indirectly pGSK3β (IC50=17 nM) and pS6 (IC50=15 nM)[1].
Cell Proliferation Assay[1] | Cell Line: | Breast tumors cell lines | | Concentration: | 0.3 nM to 50 M | | Incubation Time: | 72 hours | | Result: | Inhibited proliferation in a dose-dependent manner. |
Western Blot Analysis[1] | Cell Line: | HCC1419 and MDA-MB-453 cells | | Concentration: | 0.3, 1 μM | | Incubation Time: | 24 hours | | Result: | Inhibited p70S6K activity and induced feedback loop phosphorylation on Akt and suppressed Akt activity in breast cancer cell lines. |
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体内研究
(In Vivo) | M2698 (10-30 mg/kg/day; PO; 28 days) results in dose-dependent inhibition of tumor growth and results in tumor regression with the highest dose of 30 mg/kg[1].
M2698 (20 mg/kg/day; PO; 4 days) has a tumor:plasma exposure ratio of 12:1 over 24 hours and leads to increased levels of pAkt in tumor tissue[1].
The mean total concentration of M2698 after 16-hour infusion in rats is 1750 ng/g and 175 ng/mL in brain and plasma, respectively[1].
M2698 (po; 1, 5, 10, or 20 mg/kg/day; for 7 days) inhibits the phosphorylation of S6 in a dose-proportional manner over time after a single administration or daily treatments over 7 days[1].
| Animal Model: | Female nude mice bearing MDA-MB-468 tumors[1] | | Dosage: | 10, 20 and 30 mg/kg | | Administration: | PO; daily; for 28 days | | Result: | Resulted in dose-dependent inhibition of tumor growth and resulted in tumor regression with the highest dose of 30 mg/kg. |
| Animal Model: | Female SCID Beige mice with MDA-MB-453 xenografted[1] | | Dosage: | 20 mg/kg (Pharmacokinetic Analysis) | | Administration: | Daily; for 4 days | | Result: | Had a tumor:plasma exposure ratio of 12:1 over 24 hours. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, protect from light, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(277.86 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2229 mL | 11.1146 mL | 22.2291 mL | | 5 mM | 0.4446 mL | 2.2229 mL | 4.4458 mL | | 10 mM | 0.2223 mL | 1.1115 mL | 2.2229 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 (protect from light, stored under nitrogen)。-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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.62 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.62 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 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.62 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.62 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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