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Thiocarbonate 4a showed a nearly identical rate to 1a ( k obs = 6.39 × 10 –4 s –1 and 6.50 × 10 –4 s –1 , respectively), but the secondary 2a (3.70 × 10 –4 s –1 ) and tertiary carbonate 3a (2.37 × 10 –4 s –1 ) revealed 42 and 63% slower decay, respectively

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5-Amino-1MQ was reported as a substrate-competitive, membrane-permeable NNMT inhibitor — meaning it competes with the enzyme’s natural substrate and can cross cell membranes to reach its intracellular target — and it became the tool compound used to ask whether pharmacologically shutting down NNMT would reproduce the striking metabolic benefits seen when the enzyme was silenced genetically