Figure 3.

PIK-75 is potent in overcoming a variety of venetoclax resistances. (A, B) In vitro efficacy of BCL2i venetoclax, PI3Ki PIK-75 and GSK1059615 in paired venetoclax-sensitive (Mino and Rec-1) and -resistant (Mino-Re and Rec1-Re) cell lines (A), and additional 8 MCL cell line panel (B) by eight-dose cell viability assay at 72 hours upon treatment. (C) In vitro efficacy of venetoclax, PIK-75 and GSK1059615 in 21 primary MCL patient samples at 24 hours upon treatment. (D) Two venetoclax-sensitive (ex vivo) patient samples (PT2 and PT3) were co-cultured with HS-5 stromal cells and supplemental cytokines for two weeks. An eight-dose 24-hour cell viability assay was conducted. Each treatment for the cell viability assay was set up in triplicate. (E) Heatmaps of IC₅₀ of venetoclax, GSK1059615 and PIK-75 in MCL cell lines and primary patient samples with/without coculture with HS-5 cells based on the data (A-D). Sensitivity to venetoclax was indicated in the right for each cell line or patient sample.