Scientific Reference
5-Amino-1MQ
Evidence profile: Predominantly preclinical
The target came first here. Nicotinamide N-methyltransferase methylates nicotinamide, sits at high levels in liver and fat tissue, and drew attention once it was tied to the intracellular balance of NAD+ and of methyl donors. 5-Amino-1MQ emerged from medicinal-chemistry work screening a series of methylquinolinium analogues against that enzyme, and is a small quinolinium cation with no peptide character. Everything published on it is preclinical — enzyme assays, cultured fat cells, and mice made obese by diet. Human data barely exist, and neither its selectivity nor its behaviour in a whole animal has been characterised to any depth.
Mechanism of Action
The reaction NNMT catalyses takes a methyl group from S-adenosylmethionine and puts it on nicotinamide, yielding 1-methylnicotinamide and S-adenosylhomocysteine. 5-Amino-1MQ is understood to sit in the enzyme's nicotinamide site and compete with the substrate for it. Both of the reaction's inputs matter downstream: SAM is the cell's methyl donor, and nicotinamide is the precursor the salvage pathway returns to NAD+. That is why inhibitors of this class have been used in cultured adipocytes and in rodents to probe how NNMT activity relates to intracellular NAD+ and SAM, and to how fat cells handle lipid. How cleanly the compound avoids other methyltransferases, and how it distributes and clears in animals, is only partly described.
Molecular Information
- Type: Small molecule (quinolinium cation)
- Molecular weight: 159.21 g/mol
- Molecular formula: C10H11N2+