A Multivariate Model of Schweinfurthin A Drug Activity
(A) Reproducibility of the data for the two schweinfurthin derivatives tested in the GDSC.
(B) Heatmap indicating Schweinfurthin A drug activity and candidate determinant gene expression in the 100 most sensitive and resistant non-hematopoietic GDSC cell lines.
(C) A statistical summary of a multivariate linear model of Schweinfurthin A response in the GDSC.
(D) Scheme of the proposed molecular pharmacology of the schweinfurthins. Schweinfurthins have been shown to inhibit PI3K/AKT signaling and cell survival by binding oxysterol-binding-protein-related proteins (ORPs) to disrupt trans-Golgi network trafficking required for robust pathway activity (Bao et al., 2015). Together with the ORPs OSBP, OSBPL3, and OSBPL10, the other candidate determinants, PLEKHO1 and THEM4, have also been implicated in PI3K/AKT signaling (Liu et al., 2013, Tokuda et al., 2007).
Plots and analyses in panels B–D are based on non-hematopoietic GDSC cell lines.