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Nature 603 , 321327 (2022)

For 5-amino-1MQ specifically: Preclinical studies have not prominently described heart rate elevation as a dominant signal The mechanism (NNMT inhibition, NAD+ preservation) does not have the same direct cardiac implications as nuclear receptor agonism Human cardiovascular data at clinically relevant exposures are limited For physicians, the current evidence base does not support a major cardiovascular safety flag, but the limited human dataset means confident statements are premature

C57BL6/J WT (Gstp1/2 +/+ ) mice and Gstp1/2 knockout (Gstp1/2 / ) mice in C57BL6/J background were provided by Professor Roland Wolf and Cancer Research UK