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Bisubstrate inhibitor 78 is an inhibitor of nicotinamide N-methyltransferase (NNMT; IC50 = 1.41 μM).1 It binds the NNMT active site in the binding pockets for the NNMT substrates S-adenosyl-L-methionine (SAM) and nicotinamide . Bisubstrate inhibitor 78 is selective for NNMT over histone-lysine N-methytransferase NSD2 and protein arginine methyltransferase 1 (PRMT1; IC50s = >50 μM for both). It reduces levels of 1-methylnicotinamide in, and inhibits proliferation of, HSC-2 oral cancer cells when used at a concentration of 100 μM.

1.Gao, Y., van Haren, M.J., Moret, E.E., et al.Bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT) with enhanced activityJ. Med. Chem.62(14)6597-6614(2019)

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