tcsc0741 Copanlisib

Copanlisib (BAY 80-6946) is a selective and ATP-competitive class-I PI3 kinases inhibitor, with IC₅₀s of 0.5, 0.7, 3.7 and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively.

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) potently inhibits the catalytic activity of the class I PI3Kα, β, γ, and δ isoforms with IC₅₀s of 0.5, 3.7, 6.4, and 0.7 nM, respectively. Copanlisib (BAY 80-6946) shows significantly weaker activity against mTOR with an IC₅₀ of 45 nM. In KPL4 cells, Copanlisib (BAY 80-6946) reduces basal levels of AKT phosphorylation at both Thr308 and Ser473 with IC₅₀ values of 0.4 and 0.6 nM, respectively. Copanlisib has mean IC₅₀ values of 19 nM against cell lines with PIK3CA-activating mutations (n = 9) and 17 nM against HER2-positive cell lines (n=7), whereas the activity in PIK3CA wild-type and HER2-negative cells is about 40-fold less potent (average IC₅₀=774 nM; n=11)^[1].

In Vivo: Copanlisib (BAY 80-6946) is highly efficacious in a variety of human tumor xenograft models derived from different tumor indications that exhibit an activated PI3K pathway. Copanlisib (BAY 80-6946) is administered at 0.5 to 6 mg/kg i.v. every second day for a total of five doses starting on day 14, following tumor cell implantation. On day 25, 3 days after the last dose, TGI rates of 77%, 84%, 99%, and 100% are observed with Copanlisib (BAY 80-6946) at doses of 0.5, 1, 3, and 6 mg/kg, respectively. Complete tumor regression is shown in 10 of 10 rats in the 3 and 6 mg/kg groups, and all rats remained tumor free at the termination of the study on day 73. Tumor growth delays more than 25 days are observed in the 0.5 and 1 mg/kg dose groups^[1].