Fig. 5: Impact of the resistance mutation I777M in p110δ on the cellular efficacy of diverse PI3Ki.
From: Functional impact and molecular binding modes of drugs that target the PI3K isoform p110δ
BaF3 cells were retrovirally transduced to stably express the p110δ-E1021 without or with additional I777M mutation for CTG assays after IL-3 withdrawal. a, b Concentration-dependent responses to the p110δ-selective PI3Ki idelalisib, duvelisib, and umbralisib (a) and to the pan-class I PI3Ki copanlisib, ZSTK474, and sonolisib (b) were recorded in isogenic BaF3 cells. Representative experiments of four repetitions are shown. Error bars indicate standard deviations among quadruplicate measurements and asterisks significant differences between wt and I777M. *p < 0.05; **p < 0.01; ***p < 0.001. c PI3Ki that showed cellular IC50 below 5 µM with BaF3 cells expressing p110δ-E1021K were arranged according to decreasing potency and compared with the corresponding IC50 values of isogenic cells with additional I777M mutation. P110δ-selective PI3Ki are printed in blue and dual PI3K-mTORi in italics. The red and blue bars indicate resistance or sensitization, respectively.
