Copanlisib

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^[1]. IC50 & Target:IC50: 0.5 nM (PI3Kα), 0.7 nM (PI3Kδ), 3.7 nM (PI3Kβ), 6.4 nM (PI3Kγ), 45 nM (mTOR)^[1] 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) 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]. 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].