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10.1016/j.bbagrm.2010.07.005 92 MaharjanS.OkuM.TsudaM.HosekiJ.SakaiY

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

[DOI] [PubMed] [Google Scholar] 4.Bohmer T, Bergrem H, Eiklid K

There is no business for Novo Nordisk in that area. Focus on obesity from the beginning (this is actually from ACQ2, a second podcast hosted by Gilbert and Rosenthal, in an episode focused on Knudsen): The target market was also obesity from the beginning, Knudsen says about GLP-1 molecules, pushing back on idea that they somehow stumbled into obesity