No. 29NNMT inhibitor · small moleculePreclinical

5-Amino-1MQ — Research Dossier

Compiled by the Nexyra Research TeamPublished 30 June 2026Last reviewed 30 June 2026

Evidence grading

Preclinical
Phase I
Phase II
Phase III
Approved

Class

Small molecule

Quinolinium compound (~286 Da) — not a peptide

Target

NNMT inhibition

Nicotinamide N-methyltransferase; elevated in aged adipose and obese muscle

Downstream

NAD⁺ / sirtuins

Preserves intracellular NAD⁺/NADH; enhances SIRT1/SIRT3 activity

Human trials

0

Mechanistically coherent rodent and in-vitro data; no human efficacy trials

5-Amino-1MQ is a small-molecule NNMT inhibitor, not a peptide — grouped with the metabolic research compounds for catalogue convenience, but with fundamentally different chemistry from the rest of this library. Its NAD⁺ axis rationale is coherent; human evidence is absent.

5-Amino-1MQ (5-amino-1-methylquinolinium) is a synthetic small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT) — approximately 286 Da as the iodide salt. It is important to be explicit: this is a small molecule, not a peptide, and has no amino-acid backbone. It is included in this journal as a metabolic research compound studied alongside peptides rather than as a peptide itself.

NNMT consumes NAD⁺ precursors by methylating nicotinamide to inactive 1-methylnicotinamide (1-MNA), and is reported to be elevated in aged adipose tissue, obese skeletal muscle, and certain tumours. The therapeutic hypothesis is that inhibiting NNMT preserves cellular NAD⁺ and downstream sirtuin activity — an approach adjacent to, but mechanistically distinct from, NAD⁺ precursor supplementation (NR/NMN supply precursors; 5-Amino-1MQ blocks an NAD⁺-consuming enzyme).


NNMT knockdown protected against diet-induced obesity in mice without reducing food intake, establishing NNMT as a metabolic target distinct from caloric-restriction and GLP-1 pathways — and providing the rationale for small-molecule NNMT inhibitors as metabolic research tools.

Kraus D et al., Nature 2014

Mechanism

By selectively inhibiting NNMT, 5-Amino-1MQ is investigated for its ability to: reduce the conversion of nicotinamide to 1-methylnicotinamide (1-MNA); preserve intracellular NAD⁺/NADH ratio; enhance sirtuin (SIRT1/SIRT3) activity and energy metabolism; and promote adipocyte lipolysis.

This places it adjacent to the NAD⁺ precursor strategy, but on the conservation rather than the supply side of NAD⁺ biology: instead of adding more substrate (NR, NMN), it blocks an enzyme that consumes it. The two strategies are mechanistically distinct and potentially complementary research tools rather than interchangeable alternatives.

Evidence base

Foundational NNMT biology

Kraus et al. (2014, Nature 508:258-262) showed that NNMT knockdown in mice protected against diet-induced obesity, establishing NNMT as a metabolic vulnerability target. This is the cornerstone paper for the entire NNMT-inhibitor therapeutic hypothesis.

Small-molecule characterisation

Neelakantan et al. and related medicinal-chemistry work characterised 5-Amino-1MQ as a cell-permeable NNMT inhibitor. In adipocyte studies it altered metabolite profiles consistent with NNMT blockade, as measured by LC-MS/MS.

Rodent metabolic endpoints

5-Amino-1MQ has been studied in diet-induced-obesity rodent models for body composition, adipose lipolysis, glucose tolerance, and skeletal-muscle ageing endpoints. There are no human clinical trials.

Regulatory status and compound classification

Not approved by the FDA, MHRA, or EMA for any indication. Material supplied for laboratory work is research-use-only and not for human or veterinary use. As a small molecule rather than a peptide, its regulatory and pharmacokinetic considerations differ from those of the peptide compounds in this library.

Evidence grade: preclinical — a mechanistically coherent target (NNMT/NAD⁺/sirtuin) with supportive rodent and in-vitro data, but no human evidence. Its small-molecule nature should be made explicit wherever it is catalogued alongside peptide research compounds.


Nexyra Lab Catalogue

This dossier covers published clinical research on 5-Amino-1MQ. Nexyra Lab supplies research-grade 5-Amino-1MQ for in vitro laboratory use.

View 5-Amino-1MQ in the Nexyra catalogue (research use only) →

References

  1. 1

    Kraus D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity Nature 2014.

  2. 2

    Neelakantan H, et al. Small-molecule NNMT inhibitors (5-amino-1MQ class) — characterisation and metabolic effects in adipocytes Biochem Pharmacol 2019.

  3. 3

    Ryu KW, et al. Metabolic regulation of transcription through compartmentalised NAD⁺ biosynthesis Science 2018.


Research & Laboratory Use Only

This dossier is compiled for research planning and educational purposes only. It summarises published scientific literature and does not constitute medical advice, dosing guidance, or a therapeutic claim. All Nexyra Lab products are for research purposes only and are not for human or veterinary use. Nothing in this document should be interpreted as recommending, endorsing, or facilitating the self-administration of any compound.

A one-time legal review of this template and disclaimer is recommended before the Journal section is made publicly accessible, given the health-adjacent nature of this content.

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