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. Author manuscript; available in PMC: 2022 Jul 23.
Published in final edited form as: Nature. 2021 Apr 26;593(7860):597–601. doi: 10.1038/s41586-021-03536-w

Fig. 1. Characterisation of the RNA methyltransferase inhibitor STM2457.

Fig. 1

a) Chemical structure of STM2457. b) Biochemical activity assay showing inhibition of the METTL3/14 enzyme complex using a dose-range of STM2457 and STM2120. c) Surface plasmon resonance (SPR) assay showing binding affinity of STM2457 to the METTL3/14 protein complex. d) SPR assay showing binding affinity to the METTL3/METTL14 protein complex is reduced in the presence of SAM, indicative of SAM-competitive binding. e) STM2457 inhibits METTL3/METTL14 selectively in a methyltransferase profiling panel of 45 RNA (red bars), DNA (green bars) and protein methyltransferases (grey bars) (red star indicates <50% activity remaining) (n=2). f) Crystal structure of METTL3/METTL14 (carbon atoms in green) in complex with STM2457 (carbon atoms in cyan). Hydrogen bonds (yellow dashed lines) and water molecules proximal to the inhibitor (red sphere) are shown (PDB code 7O2I). g) Quantification of m6A levels on poly-A+-enriched RNA after 24 hours of treatment of MOLM-13 with the indicated STM2457 concentrations (mean +/- s.d., n=3). IC50, half maximum inhibitory concentration.