Copanlisib dihydrochloride

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) 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 dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib dihydrochloride has superior antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

PI3Kα:0.5 nM (IC50)

PI3Kδ:0.7 nM (IC50)

PI3Kβ:3.7 nM (IC50)

PI3Kγ:6.4 nM (IC50)

mTOP:45 nM (IC50)

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 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[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 an EC50 of 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.

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.

[1]. Liu N, et al. BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models. Mol Cancer Ther. 2013 Nov;12(11):2319-30.