PKI-179 是一种有效的和具有口服活性的双重PI3K/mTOR抑制剂，对PI3K-α，PI3K-β，PI3K-γ，PI3K-δ和mTOR的IC50值分别为 8 nM，24 nM，74 nM，77 nM 和 0.42 nM。PKI-179 还表现出对E545K和H1047R的活性，IC50值分别为 14 nM 和 11 nM。PKI-179 在体内显示出抗肿瘤活性。
| 生物活性 | PKI-179 is a potent and orally active dualPI3K/mTORinhibitor, withIC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM forPI3K-α,PI3K-β,PI3K-γ,PI3K-δandmTOR, respectively. PKI-179 also exhibits activity overE545KandH1047R, withIC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2]. |
| IC50& Target[1] | PI3Kα 8 nM (IC50) | PI3Kβ 24 nM (IC50) | PI3Kγ 74 nM (IC50) | PI3Kδ 77 nM (IC50) | mTOR 0.42 nM (IC50) | E545K 14 nM (IC50) | H1047R 11 nM (IC50) |
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体外研究
(In Vitro) | PKI-179 inhibits the cell proliferation, with IC50s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively[1].
PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC50=3 μM)[1].
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体内研究
(In Vivo) | PKI-179 (5-50 mg/kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors[1].
PKI-179 (50 mg/kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts[1].
PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min)[1].
| Animal Model: | Nude mice bearing MDA-361 human breast cancer tumors[1] | | Dosage: | 5, 10, 25, 50 mg/kg | | Administration: | I.p. every 3 days for 4 weeks | | Result: | Exhibited pronounced tumor growth arrest when dosed above 10 mg/kg.
No significant weight loss of tested animals was observed for all different dosages. |
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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 : 100 mg/mL(204.69 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.0469 mL | 10.2346 mL | 20.4692 mL | | 5 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL | | 10 mM | 0.2047 mL | 1.0235 mL | 2.0469 mL |
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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： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.12 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.12 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.12 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.12 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 25.0 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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