Fig. 4: Influence of MTA on PRMT5 inhibitor engagement.
From: A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells
A–F Representative compound concentration curves for PRMT5 inhibitors under low and high MTA concentration. HEK293 cells were treated with 30 nM CBH-002, a 300 μM, 7 pt, 3-fold series of MTA, and an 11 pt, 3-fold series of PRMT5 inhibitor for 2 h prior to BRET measurements. Vehicle treatment and 300 μM MTA conditions shown (see Fig. S4 for full dataset). Data are the mean ± SEM of 3 independent experiments (n = 3). Cofactor competitive (A, B) and SAM-uncompetitive (C, D) inhibitors exhibit weakened affinity in the presence of high [MTA]. MTA-cooperative inhibitors (E, F) exhibit enhanced potency in the presence of high [MTA]. G EC50 shift fold-change for PRMT5 inhibitors. Values were calculated as the difference between compound EC50 at 300 μM MTA and compound EC50 with vehicle treatment. Negative values represent compounds which experienced enhanced potency under high MTA conditions. Source data are provided as a Source Data file.
