Copanlisib (BAY 80-6946) 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 对其他脂质和蛋白激酶的选择性超过 2000 倍。Copanlisib 具有优异的抗肿瘤活性。
| 生物活性 | Copanlisib (BAY 80-6946) 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 has more than 2,000-fold selectivity against other lipid and protein kinases, except formTOR. Copanlisib has superior antitumor activity[1]. |
| IC50& Target[1] | PI3Kα 0.5 nM (IC50) | PI3Kβ 3.7 nM (IC50) | PI3Kδ 0.7 nM (IC50) | PI3Kγ 6.4 nM (IC50) | mTOR 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 | | 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: 1M HCl : 100 mg/mL(208.11 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.0811 mL | 10.4054 mL | 20.8108 mL | | 5 mM | 0.4162 mL | 2.0811 mL | 4.1622 mL | | 10 mM | 0.2081 mL | 1.0405 mL | 2.0811 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。 |
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