Copanlisib dihydrochloride

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC 50 s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα , PI3Kδ , PI3Kβ and PI3Kγ , respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR . Copanlisib dihydrochloride has superior antitumor activity 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. 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 IC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Apoptosis AnalysisCell 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 EC 50 of 340 nM. Western Blot AnalysisCell 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. 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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. IC50& Target:PI3Kα 0.5 nM (IC 50 ) PI3Kδ 0.7 nM (IC 50 ) PI3Kβ 3.7 nM (IC 50 ) PI3Kγ 6.4 nM (IC 50 ) mTOP 45 nM (IC 50 )

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