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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

Extended Data Figure. 1. STM2457 is a specific small molecule inhibitor of METTL3 with no evidence of off-target effects.

Extended Data Figure. 1

a) Chemical structures of STM1760 and STM2120. b) Biochemical activity assay showing inhibition of the METTL3/METTL14 enzyme complex using a dose-range of STM1760. c) Surface plasmon resonance (SPR) sensorgram showing the binding of STM2457 to the METTL3/METTL14 protein complex. d) SPR sensorgram showing reduced binding of STM2457 to the METTL3/METTL14 protein complex in the presence of 50 µM SAM, illustrating that STM2457 is SAM competitive. e) SPR assay showing single-cycle binding kinetics of STM2457. f) Biochemical activity assay showing no inhibition of METTL16, NSUN1 and NSUN2 RNA methyltransferases using a dose-range of STM2457. g) Methyltransferase dendrograms showing that 10 µM STM2457 has selective inhibitory activity for METTL3/METTL14 over the indicated RNA and protein methyltransferases. h) Treatment with 10 µM STM2457 did not inhibit (ie result in less than 50% control activity) any of the 468 kinases in the ScanMax (DiscoverX) kinase panel tested (marked by green dots).