Scientific Reference
5-Amino-1MQ
Evidence profile: Predominantly preclinical
5-Amino-1MQ is a small quinolinium molecule, not a peptide, designed to inhibit the enzyme nicotinamide N-methyltransferase (NNMT). It came out of medicinal-chemistry work on a series of methylquinolinium analogues screened against that enzyme, which methylates nicotinamide and is expressed at high levels in liver and fat tissue. Interest in NNMT grew once it was linked to the balance of NAD+ and of methyl donors inside cells. Published work on 5-Amino-1MQ is preclinical: enzyme assays, cultured fat cells and diet-induced obese mouse models. Human data are very limited, and its selectivity and behaviour in the whole organism are not well characterised.
Mechanism of Action
NNMT transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide, producing 1-methylnicotinamide and S-adenosylhomocysteine. 5-Amino-1MQ is thought to occupy the enzyme's nicotinamide site and compete with the natural substrate. Because the reaction consumes both SAM and nicotinamide, a precursor recycled into NAD+ through the salvage pathway, inhibitors of this kind have been used in cultured adipocytes and rodent studies to examine how NNMT activity relates to intracellular NAD+ and SAM levels and to lipid handling in fat cells. How selective the compound is across other methyltransferases, and how it is distributed and cleared in animals, has been only partly described.
Molecular Information
- Type: Small molecule (quinolinium cation)
- Molecular weight: 159.21 g/mol
- Molecular formula: C10H11N2+