Fig. 7: Cryo-EM SBDD yields 11-2F analogs of higher potency in PRMT5 inhibition. | Communications Biology

Fig. 7: Cryo-EM SBDD yields 11-2F analogs of higher potency in PRMT5 inhibition.

From: Cryo-EM structure-based selection of computed ligand poses enables design of MTA-synergic PRMT5 inhibitors of better potency

Fig. 7

Three different compounds were selected based on docking analysis. 11-9 F (a), HWIem2104 (b), and HWIem2109 (c) are showed in the binding pockets with key residues contributing to their stability. d Comparison of relative docking free energy among the four compounds. e The chemical structure of 11-9F (left) and its dose-dependent inhibition of PRMT5: MEP50 enzyme activity, yielding an IC50 ~ 180 nM. Error bars: s.d. (n = 3). f Western blotting of SDMA in cells treated with 11-9 F in different concentrations with 0 and 5.0 μM MTA. g Individual bands were digitized in ImageJ, calibrated against the actin bands, and then normalized against 0 μM 11-9 F in order to generate the two plots (red vs. black). Error bars: s.d., n = 3. The relative inhibition data were fitted with an equation I = 1/(1 + [L] / IC50) to IC50 of 2.4 (red trace) and 32.4 (black trace) μM, respectively. The coupling factor between MTA and 11-9F is ~10, an indicator of strong synergy.

Back to article page