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Pulse Research // 024  ·  LONGEVITY RESEARCH

Not a peptide. An enzyme question.

Cells spend a vitamin-derived building block in two directions. 5-Amino-1MQ is studied as a way of blocking the enzyme that diverts it.

5-Amino-1MQ  ·  NNMT-inhibitor small molecule

In plain terms

Nicotinamide, a form of vitamin B3, is the raw material for NAD+, the molecule cells use to carry electrons when they make energy. An enzyme called NNMT consumes nicotinamide instead, and it is more active in fat tissue in obesity. 5-Amino-1MQ is studied as an inhibitor of that enzyme. The evidence so far is from cultured cells and mice.

What it is

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small synthetic molecule, not a peptide. It belongs to a series of methylquinolinium compounds developed at the University of Texas Medical Branch and is studied as an inhibitor of nicotinamide N-methyltransferase, or NNMT (Neelakantan et al. 2017).

NNMT is an enzyme that takes a methyl group from S-adenosylmethionine (SAM), the cell’s main methyl donor, and attaches it to nicotinamide. That reaction uses up two things at once: the nicotinamide that would otherwise be recycled into NAD+, and the SAM that is needed for many other methylation reactions. The research premise is that inhibiting NNMT leaves more of both available inside the cell. NNMT expression is raised in fat tissue in mouse models of obesity, and lowering it protected mice against diet-induced obesity, which is what made the enzyme a target (Kraus et al. 2014).

What research has examined

The compound paper used cultured mouse adipocytes (fat cells) and diet-induced obese mice. In cells, the methylquinolinium inhibitors crossed membranes, were selective for NNMT over related methyltransferases and NAD+ salvage enzymes, lowered the NNMT product 1-methylnicotinamide, raised intracellular NAD+ and SAM, and reduced fat synthesis. In mice on a high-fat diet, systemic treatment reduced body weight, white fat mass and plasma cholesterol without a change in food intake (Neelakantan et al. 2018). A later study from the same group examined muscle stem cells from aged mice and reported improved regenerative capacity after injury (Neelakantan et al. 2019).

Related-target research, not research on this compound: a separate industry group reported a structurally different NNMT inhibitor, JBSNF-000088, which reduced body weight and improved glucose handling in obese mice and had no effect in mice lacking NNMT, supporting the enzyme as the relevant target (Kannt et al. 2018). That paper did not test 5-Amino-1MQ.

No human trial of 5-Amino-1MQ has been published.

What remains uncertain

All results are preclinical: cells and mice, mostly from the originating laboratory. Effects on body weight in mice on a high-fat diet do not predict effects in people, and the changes in NAD+ and SAM were measured inside cultured cells rather than in human tissue.

Pharmacokinetics, long-term exposure and off-target effects in humans have not been described. NNMT also has roles in the liver and in clearing nicotinamide, so the consequences of inhibiting it broadly are not settled. As a small molecule rather than a peptide, the material differs in handling and analysis from most of the catalogue.

How it relates to other research

Sources

  1. Neelakantan H et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. Journal of Medicinal Chemistry, 2017.cell study
  2. Neelakantan H et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochemical Pharmacology, 2018.animal study
  3. Neelakantan H et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochemical Pharmacology, 2019.animal study
  4. Kraus D et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature, 2014.animal study
  5. Kannt A et al. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Scientific Reports, 2018.animal study

Status

5-Amino-1MQ is not an approved medicine in Australia (no ARTG entry identified) and has no marketing approval identified elsewhere; it is an investigational small molecule with no published human trials.

Sources and status checked 2026-09-22

5-Amino-1MQ — sizes and pricing
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