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MetabolicPreclinical only

5-Amino-1MQ

Published research and evidence base

5-Amino-1MQ (5-amino-1-methylquinolinium) is a cell-permeable small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the enzyme that methylates nicotinamide and thereby consumes S-adenosylmethionine and diverts nicotinamide away from NAD+ salvage. Interest in the target followed a 2014 Nature report that antisense knockdown of NNMT in adipose tissue and liver protected mice against diet-induced obesity. Subsequent work characterised 5-amino-1MQ and related quinolinium inhibitors in diet-induced obese rodents, aged skeletal muscle, sarcopenia and peripheral artery disease models, alongside medicinal-chemistry and mechanism-of-inhibition studies. The published evidence base is entirely preclinical; no human clinical trial of 5-amino-1MQ has been reported in the peer-reviewed literature.

Studies cited
15
Published 2023+
8
Newest paper
2026
Last reviewed
Aug 2026

Recurring themes in the literature

  • NNMT inhibition and NAD+ salvage pathway flux
  • Adipose tissue NNMT expression and diet-induced obesity in rodents
  • Skeletal muscle stem cell function, aged muscle regeneration and sarcopenia
  • S-adenosylmethionine consumption and polyamine flux
  • 1-methylnicotinamide as a biomarker of NNMT activity
  • Medicinal chemistry: selectivity, membrane permeability and inhibitor turnover
  • Combination with calorie restriction or exercise in rodent models
  • Absence of human clinical data

Compound identifiers

CAS
685079-15-6
PubChem
950107
Chemical identity

What 5-Amino-1MQ is, chemically.

Molecular formula
C10H11N2+
Molecular weight
159.21 g/mol
CAS number
685079-15-6
PubChem CID
950107
Also written as

5-amino-1-methylquinolinium

These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.

The evidence

15 published studies.

Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.

  1. 01Animal in vivo2025

    Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease

    Dong G, et al. · Physiological Reports · mouse hindlimb ischaemia model of peripheral artery disease treated with an NNMT inhibitor

    NNMT inhibitor treatment enhanced muscle strength and treadmill performance in mice with hindlimb ischaemia. The functional gains occurred independently of perfusion recovery.

  2. 02Animal in vivo2024

    Identification of nicotinamide N-methyltransferase as a promising therapeutic target for sarcopenia

    Liang R, et al. · Aging Cell · aged mice with age-related muscle loss, treated with NNMT inhibition

    NNMT inhibition improved grip strength and muscle mass in aged mice. The effects were associated with increased NAD+ levels and AMPK activation in skeletal muscle.

  3. 03Animal in vivo2024

    Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice

    Dimet-Wiley AL, et al. · Scientific Reports · aged sedentary and exercised mice treated with an NNMT inhibitor

    NNMT inhibition produced grip strength gains of roughly 40% in aged sedentary mice. Benefits were additive when the inhibitor was combined with exercise training.

  4. 04Animal in vivo2024

    Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction

    Babula JJ, et al. · Diabetes, Obesity & Metabolism · diet-induced obese mice dosed with 5-amino-1MQ (5A1MQ) across a dose range

    5-amino-1MQ dose-dependently reduced body weight and improved glucose tolerance in diet-induced obese mice. Liver histopathology also improved relative to vehicle-treated controls.

  5. 05Animal in vivo2022

    Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders

    Ruf S, et al. · Scientific Reports · medicinal-chemistry series evaluated in vitro and in obese mice (lead compound JBSNF-000028)

    A tricyclic NNMT inhibitor series reduced 1-methylnicotinamide levels and improved insulin sensitivity and body weight in obese mice. The work extended NNMT inhibitor chemotypes beyond the quinolinium scaffold.

  6. 06Animal in vivo2021

    Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice

    Sampson CM, et al. · Scientific Reports · diet-induced obese mice receiving an NNMT inhibitor alone, calorie restriction alone, or both

    Combining NNMT inhibition with a reduced-calorie diet normalised body composition and hepatic adiposity more completely than diet alone. The combination produced greater metabolic improvement than either intervention independently.

  7. 07Animal in vivo2019

    Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle

    Neelakantan H, et al. · Biochemical Pharmacology · aged mouse skeletal muscle and isolated muscle stem cells treated with a small-molecule NNMT inhibitor

    NNMT inhibition activated senescent muscle stem cells and improved regenerative capacity in aged skeletal muscle. Contractile force recovery after injury increased by approximately 70% relative to control.

  8. 08Animal in vivo2018

    Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice

    Neelakantan H, et al. · Biochemical Pharmacology · diet-induced obese mice dosed with the quinolinium NNMT inhibitor 5-amino-1MQ

    Systemic administration of the selective, membrane-permeable NNMT inhibitor reduced body weight and adiposity in diet-induced obese mice without reducing food intake. Treatment raised adipose NAD+ and suppressed lipogenic gene expression.

  9. 09Animal in vivo2018

    A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders

    Kannt A, et al. · Scientific Reports · diet-induced obesity models treated with the NNMT inhibitor JBSNF-000088

    The inhibitor reduced tissue 1-methylnicotinamide, lowered body weight and normalised glucose tolerance in obese rodents. The report provided independent pharmacological confirmation of NNMT as a metabolic target.

  10. 10Animal in vivo2014

    Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity

    Kraus D, et al. · Nature · antisense oligonucleotide knockdown of NNMT in adipose tissue and liver of diet-induced obese mice

    NNMT knockdown protected mice against diet-induced obesity and increased energy expenditure without altering food intake. The authors attributed the effect to increased adipose polyamine flux and altered NAD+ and S-adenosylmethionine handling, establishing NNMT as a metabolic drug target.

  11. 11In vitro2025

    Mechanism and kinetics of turnover inhibitors of nicotinamide N-methyl transferase in vitro and in vivo

    Akerud T, et al. · Journal of Biological Chemistry · enzyme kinetics and mechanistic studies in vitro, with confirmatory rat pharmacology

    The study reported that certain NNMT inhibitors are themselves substrates that undergo enzymatic turnover, generating methylated metabolites that are more potent inhibitors than the parent compound. Rat experiments indicated the mechanism operates in vivo.

  12. 12Review2026

    Emerging opportunities for nicotinamide N-methyltransferase (NNMT) inhibitor clinical translation

    Puleo N, et al. · Trends in Pharmacological Sciences · review of NNMT inhibitor pharmacology, medicinal chemistry and translational prospects

    The review assessed the therapeutic potential of NNMT inhibitors across diabetes, obesity, fibrosis and cancer and summarised recent advances in inhibitor design. It framed clinical translation as an emerging rather than established prospect.

  13. 13Review2025

    Nicotinamide N-Methyltransferase in Cardiovascular Diseases: Metabolic Regulator and Emerging Therapeutic Target

    Jawaria, et al. · Biomolecules · narrative review of NNMT in cardiovascular pathophysiology

    The review described NNMT's contribution to cardiovascular disease through NAD+ depletion and homocysteine elevation. It catalogued preclinical evidence for therapeutic benefit from NNMT inhibition while noting the absence of clinical confirmation.

  14. 14Review2024

    Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

    Sun WD, et al. · Frontiers in Pharmacology · narrative review of NNMT in obesity, insulin resistance, dyslipidaemia and hepatic steatosis

    The review linked elevated NNMT expression to features of metabolic syndrome across rodent and human tissue studies. It summarised knockdown and inhibitor data showing enhanced energy expenditure and insulin sensitivity in rodent models.

  15. 15Review2017

    Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme

    Pissios P · Trends in Endocrinology and Metabolism · mechanistic review of NNMT biology across adipose, liver and tumour tissue

    The review set out NNMT's roles beyond vitamin B3 clearance, including regulation of the methylation potential and NAD+ availability. It summarised evidence linking NNMT expression to obesity, insulin resistance and cancer metabolism.

Limitations

What this evidence does not establish.

No human clinical trial of 5-amino-1MQ has been published; every efficacy finding in this set derives from rodent models or in vitro enzymology, and human pharmacokinetics, oral bioavailability, safety and dosing are uncharacterised in the peer-reviewed literature. Long-term consequences of sustained NNMT inhibition on methylation potential, polyamine metabolism and tumour biology are also unresolved, and no biomarker-controlled human study has confirmed target engagement.

Common questions about the research.

What is 5-Amino-1MQ?

5-Amino-1MQ is a membrane-permeable small molecule that inhibits nicotinamide N-methyltransferase (NNMT), an enzyme linking methylation metabolism to the NAD+ salvage pathway. Unlike most compounds in this catalogue it is not a peptide.

Why is an NNMT inhibitor studied in metabolic research?

NNMT consumes both S-adenosylmethionine and nicotinamide, so its activity influences methyl-donor availability and NAD+ salvage. Genetic knockdown of the enzyme in mice altered adipose SAM and NAD+ levels and changed metabolic phenotypes, which motivated the search for small-molecule inhibitors such as 5-Amino-1MQ.

Which route appears in the research literature?

The published preclinical studies dosed the compound orally in rodents on a per-kg basis over multi-week protocols. There is no human dosing literature for 5-Amino-1MQ.

Has 5-Amino-1MQ been tested in humans?

No human clinical trial of 5-amino-1MQ has been published. Every efficacy finding in the literature derives from rodent models or in vitro enzymology, and human pharmacokinetics, oral bioavailability, safety and dosing are uncharacterised in the peer-reviewed record. No biomarker-controlled human study has confirmed target engagement, and the long-term consequences of sustained NNMT inhibition for methylation potential, polyamine metabolism and tumour biology remain unresolved.

For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.