Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) 是一种有效的，选择性的和 ATP 竞争性的泛 I 类PI3K抑制剂，对PI3Kα，PI3Kδ，PI3Kβ和PI3Kγ的IC50分别为 0.5 nM、0.7 nM、3.7 nM 和 6.4 nM。除 mTOR 外，Copanlisib dihydrochloride 对其他脂质和蛋白激酶的选择性超过 2000 倍。Copanlisib dihydrochloride 具有优异的抗肿瘤活性。
| 生物活性 | Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class IPI3Kinhibitor, withIC50s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM forPI3Kα,PI3Kδ,PI3KβandPI3Kγ, respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except formTOR. Copanlisib dihydrochloride has superior antitumor activity[1]. |
| IC50& Target[1] | PI3Kα 0.5 nM (IC50) | PI3Kδ 0.7 nM (IC50) | PI3Kβ 3.7 nM (IC50) | PI3Kγ 6.4 nM (IC50) | mTOP 45 nM (IC50) |
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体外研究
(In Vitro) | Copanlisib (BAY 80-6946; 20-200 nM; 24 hours; BT20 breast cancer cells) treatmemnt induces apoptosis in a subset of tumor cell lines that are resistant to Lapatinib and Trastuzumab[1].
Copanlisib (BAY 80-6946; 0.5-500 nM; 2 hours; ELT3 cells) treatmemnt shows complete inhibition of PI3K-mediated AKT phosphorylation in ELT3 cells[1].
Copanlisib potently inhibits cell proliferation in a panel of human tumor cell lines. Copanlisib has meanIC50values of 19 nM against cell lines with PIK3CA-activating mutations and 17 nM against HER2-positive cell lines, whereas the activity in PIK3CA wild-type and HER2-negative cells is about 40-fold less potent[1].
Apoptosis Analysis[1] | Cell Line: | BT20 breast cancer cells | | Concentration: | 20 nM and 62 nM, 200 nM | | Incubation Time: | 24 hours | | Result: | Significantly increased caspase9 activities. Also increased levels of phosphorylated p53 at Ser15and cleaved PARP. Induced caspase-9 activation with anEC50of 340 nM. |
Western Blot Analysis[1] | Cell Line: | ELT3 cells | | Concentration: | 0.5 nM, 5 nM, 50 nM, 500 nM | | Incubation Time: | 2 hours | | Result: | Complete inhibition of PI3K-mediated AKT phosphorylation was clearly shown at a concentration of 5 nM. |
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体内研究
(In Vivo) | Copanlisib (BAY 80-6946; 0.5-6 mg/kg; intravenous injection; every second day, every third day; for 60 days; athymic nude rats) treatment displays robust antitumor activity in the rat KPL4 tumor xenograft model[1].
| Animal Model: | Athymic nude rats injected with KPL4 tumor cells[1] | | Dosage: | 0.5 mg/kg, 1 mg/kg, 3 mg/kg or 6 mg/kg | | Administration: | Intravenous injection; every second day, every third day; for 60 days | | Result: | On day 25, tumor growth inhibition (TGI) rates of 77%, 84%, 99%, and 100% were observed at doses of 0.5, 1, 3, and 6 mg/kg, respectively. All rats remained tumor free at the termination of the study on day 73. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: H2O : 20 mg/mL(36.14 mM;Need ultrasonic) DMSO : 5 mg/mL(9.03 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.8069 mL | 9.0344 mL | 18.0688 mL | | 5 mM | 0.3614 mL | 1.8069 mL | 3.6138 mL | | 10 mM | 0.1807 mL | 0.9034 mL | 1.8069 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 (sealed storage, away from moisture)。-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： PBS Solubility: 100 mg/mL (180.69 mM); Clear solution; Need ultrasonic
*以上所有助溶剂都可在本网站选购。 |
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