Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase

Bioorg Med Chem Lett. 2018 Mar 1;28(5):922-925. doi: 10.1016/j.bmcl.2018.01.058. Epub 2018 Jan 31.

Abstract

Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ∼80% at 2 h when dosed in mice orally at 50 mg/kg.

Keywords: Diabetes; Methyl-nicotinamide (MNA); Ncotinamide; Nicotinamide N-methyltransferase (NNMT); Obesity.

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Niacinamide / chemical synthesis
  • Niacinamide / chemistry
  • Niacinamide / pharmacology*
  • Nicotinamide N-Methyltransferase / antagonists & inhibitors*
  • Nicotinamide N-Methyltransferase / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Niacinamide
  • Nicotinamide N-Methyltransferase