Copanlisib (BAY 80-6946) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC50s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib has superior antitumor activity.
体外研究
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.
Copanlisib (BAY 80-6946; 0.5-500 nM; 2 hours; ELT3 cells) treatmemnt shows complete inhibition of PI3K-mediated AKT phosphorylation in ELT3 cells.
Copanlisib potently inhibits cell proliferation in a panel of human tumor cell lines. Copanlisib has mean IC50 values 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.
Apoptosis Analysis
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 an EC50 of 340 nM.
Western Blot Analysis
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.
体内研究
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.
Animal Model:
Athymic nude rats injected with KPL4 tumor cells
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.
分子式
C23H28N8O4
分子量
480.52
CAS号
1032568-63-0
中文名称
库潘尼西
运输条件
Room temperature in continental US; may vary elsewhere.