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NAD+ BENEFITS Selective NNMT inhibition substrate-site targeting with minimal off-target activity in preclinical models NAD+ salvage modulation studied for increasing intracellular NAD+ and SAM availability Adipose metabolism investigated for suppression of adipocyte lipogenesis in 3T3-L1 models Small molecule distinct mechanism from peptide-based metabolic compounds (GLP-1 agonists, etc.) Defined pharmacology IC of 1.2 M confirmed in published enzymatic assays WHAT RESEARCHERS LOOK AT NNMT enzyme inhibition kinetics and SAM/1-MNA substrate balance NAD+ and SAM level changes in adipocyte and hepatocyte cell models Lipogenesis suppression in 3T3-L1 differentiated adipocyte assays Polyamine flux enzyme upregulation (ODC, SSAT) and histone methylation In vivo efficacy in diet-induced obesity (DIO) murine models

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Key finding: AOD 9604 reduced cartilage damage score by 67%, decreased MMP-13 activity by 58%, and preserved joint space width

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