5-Amino-1MQ

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small molecule inhibitor of Nicotinamide N-methyltransferase (NNMT), an enzyme that catalyzes the methylation of nicotinamide using S-adenosyl methionine (SAM) as the methyl donor, producing 1-methylnicotinamide and S-adenosyl homocysteine. NNMT is highly expressed in adipose tissue in obesity and is considered a key regulator of the methionine cycle, cellular methylation capacity, and NAD+ biosynthesis.

The research rationale for 5-Amino-1MQ stems from work by Kraus and colleagues at Duke University demonstrating that NNMT knockout or inhibition in mice produced striking reductions in adipocyte size and fat mass, with protection against diet-induced obesity. The mechanism involves NNMT's role in regulating the SAM/SAH ratio: elevated NNMT activity in obese adipose tissue depletes SAM, impairing histone and DNA methylation in fat cells, while also reducing nicotinamide available for NAD+ synthesis. NNMT inhibition restores these metabolic parameters.

5-Amino-1MQ is membrane-permeable and has been studied in cell culture and mouse models. Research has documented that 5-Amino-1MQ treatment of adipocytes reduces cell size, increases NAD+ content, activates SIRT1, and alters expression of adipogenic transcription factors (PPARγ, C/EBPα). In diet-induced obesity mouse models, 5-Amino-1MQ administration reduced weight gain and improved metabolic parameters without reducing food intake in some study designs.

This compound occupies an interesting intersection between epigenetics research and metabolic pharmacology, as NNMT links the methionine cycle to both NAD+ availability and histone methylation status. 5-Amino-1MQ is available for research use only. The body of literature remains primarily preclinical but is growing rapidly given interest in NNMT as a therapeutic target.