5-Amino-1MQ and the NNMT Inhibitor Family: A Research Review of Quinolinium, Substrate-Analogue and Bisubstrate Scaffolds and the Catalogue Nomenclature Behind the "Peptide" Label

By the Peptide Insider Research Desk · 12 min read · Last updated: September 12, 2026

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the cytosolic enzyme that transfers a methyl group from S-adenosyl-L-methionine (SAM) onto nicotinamide to produce 1-methylnicotinamide (1-MNA) [1,2]. Although research catalogues list the compound as a 5 amino 1mq peptide or 5-amino-1mq peptide, it contains no amino acids and no amide backbone; it is a permanently cationic quinolinium salt discovered through a medicinal-chemistry screen at the University of Texas Medical Branch [2]. This review places 5-amino 1mq in the context of the wider NNMT-inhibitor family — quinolinium analogues, the substrate-analogue JBSNF-000088 series and the bisubstrate NS1 class — and documents the notation variants under which the compound is catalogued. All content is provided strictly for research reference.

Introduction

Few compounds in the research-peptide catalogue illustrate the gap between chemistry and labelling as clearly as 5-Amino-1MQ. The compound emerged from a 2017 structure-activity relationship (SAR) campaign in which quinolinium, isoquinolinium, pyridinium and benzimidazolium analogues of nicotinamide were screened against recombinant human NNMT [2]. Quinolinium scaffolds bearing a primary amine produced the most potent hits, and 5-amino-1-methylquinolinium became the reference tool compound for the series [1,2]. Its placement in supplier listings beside genuine peptides such as MOTS-c explains the chemically incorrect "peptide" suffix.

This article is a companion to the site's single-compound 5-Amino-1MQ review. It addresses three questions: what NNMT actually does, how the different inhibitor chemotypes differ from one another, and how to interpret the many catalogue notations — from "5-amino" to "5amino-1mq" — that refer to the same cation.

Biological background: the NNMT reaction and its two products

NNMT (EC 2.1.1.1) was cloned from human liver in 1994 and characterised as a 264-residue cytosolic methyltransferase with a Rossmann-fold SAM-binding domain [3]. The enzyme catalyses a single reaction: nicotinamide + SAM → 1-methylnicotinamide (1-MNA) + S-adenosyl-L-homocysteine (SAH) [3,4]. Long read as vitamin B3 clearance [5], the reaction was reinterpreted after three findings.

• The methylation-sink concept. Ulanovskaya, Zuhl and Cravatt reported in 2013 that NNMT over-expression in cancer cell lines depleted SAM, raised SAH and produced widespread hypomethylation of histones and signalling proteins, coining the term "metabolic methylation sink" [6].
• Adipose energy expenditure. Kraus and colleagues reported in 2014 that Nnmt was the most strongly regulated gene in white adipose tissue of Glut4-modified mice and that antisense knockdown of Nnmt protected mice against diet-induced obesity, an effect linked to increased polyamine flux and NAD+-dependent SIRT1 signalling [7].
• Tissue-specific divergence. Hong and colleagues reported in 2015 that hepatic NNMT and its product 1-MNA stabilise SIRT1 protein in the liver, a context in which NNMT activity appeared metabolically favourable [8].

Because NNMT consumes both nicotinamide (the NAD+ salvage precursor) and SAM (the universal methyl donor), inhibiting the enzyme has been hypothesised to raise both pools simultaneously, a mechanism distinct from direct NAD+ precursor supplementation [1,5].

Structure and mechanism of 5-Amino-1MQ

5-Amino-1MQ is a bicyclic quinoline in which the ring nitrogen is quaternised by a methyl group, giving a permanent positive charge, and position 5 of the benzo ring carries a primary amine [2]. In the 2017 SAR study the cationic nitrogen was identified as the critical pharmacophore: docking into the nicotinamide pocket of NNMT placed the quinolinium cation where the pyridinium ring of the natural product 1-MNA would sit, and predicted docking scores correlated with measured IC₅₀ values across a >1000-fold activity range [2]. The compound is therefore classified as a nicotinamide-competitive, substrate-site inhibitor.

In the 2018 follow-up, the amine-substituted quinolinium series showed high permeability in parallel artificial membrane and Caco-2 assays and did not inhibit structurally related SAM-dependent methyltransferases or NAD+ salvage enzymes at the concentrations tested [1]. In cultured 3T3-L1 adipocytes, treatment lowered intracellular 1-MNA and raised intracellular NAD+ and SAM, consistent with on-target inhibition [1].

Nomenclature and catalogue variants

The compound's name lends itself to unusual notational drift because it combines a positional prefix ("5-amino"), a locant ("1") and an abbreviation ("MQ" for methylquinolinium). The table interprets the variants that appear in research catalogues and search queries; none of them is a chemically distinct entity.

Catalogue / query string	Interpretation	Notes
5-amino-1mq	Standard hyphenated abbreviation	Reference form used in most listings; the "MQ" stands for 1-methylquinolinium.
5 amino 1mq · 5-amino 1mq · 5 amino 1 mq	Space/hyphen variants	Identical cation; punctuation only.
5amino1mq · 5amino 1mq · 5amino-1mq	Concatenated variants	Search-engine style with the space after "5" removed.
5-amino-1q · 5 amino 1q	Truncated variants	The "M" (methyl) is dropped; still refers to 5-amino-1-methylquinolinium.
5-amino · 5 amino · 5amino	Prefix-only shorthand	Ambiguous in chemistry (many 5-amino compounds exist) but used in peptide catalogues to mean this compound.
5 amino 1mq peptide · 5-amino-1mq peptide · 5-amino 1mq peptide · 5 amino 1mq peptides	"Peptide" suffix	Chemically incorrect: the molecule has no amino-acid residues. Reflects placement in peptide catalogues.
5 amino peptide · 5-amino peptide	Prefix + "peptide" suffix	Same misnomer with the locant dropped.
5-amino-1mq 50mg	Vial-size catalogue listing	Describes the quantity of lyophilised material in a research vial, not any protocol.
what is 5 amino 1mq · what does 5 amino 1mq do	Question-form queries	Answered in the FAQ below.
5 amino 1mq reddit	Discussion-forum query	Refers to anecdotal forum threads, which are not a substitute for the peer-reviewed literature cited here.

The NNMT inhibitor family: how the chemotypes differ

Three inhibitor classes dominate the published literature. They share a target but differ in binding mode, potency and cell permeability.

Class (example)	Binding mode	Reported potency	Key reference
Quinolinium cations (5-Amino-1MQ)	Nicotinamide-site competitive	IC50 ≈ 1 µM; cell-permeable	Neelakantan 2017, 2018 [1,2]
Substrate analogues (JBSNF-000088)	Slow-turnover substrate; methylated by NNMT and blocks the catalytic cycle	Sub-micromolar; orally active in mice	Kannt 2018 [9]
Bisubstrate conjugates (NS1)	Spans both nicotinamide and SAM pockets via an alkynyl linker	Sub-nanomolar affinity; limited permeability	Policarpo 2019 [10]

JBSNF-000088 is a nicotinamide analogue developed by Sanofi. Co-crystal structures showed it bound in the nicotinamide pocket and was itself methylated slowly, reducing 1-MNA output; in diet-induced obese mice the compound reduced body weight and normalised glucose tolerance, and these effects were absent in Nnmt-knockout mice, which established target specificity [9]. NS1, by contrast, was designed to mimic the linear transition state of methyl transfer: a nicotinamide unit and a SAM-like adenosine are joined by an alkyne that spans the methyl-transfer tunnel, producing the most potent NNMT inhibitor reported at the time [10]. Its polarity limits cellular uptake, so the quinolinium series remains the usual cell-based tool [1,10].

Evidence by research domain

Domain	Model	Principal observation	Ref.
Adipocyte biology	3T3-L1 cells	Reduced lipogenesis; lower 1-MNA; higher NAD+ and SAM	[1]
Diet-induced obesity	C57BL/6 mice on high-fat diet	Lower body weight and white adipose mass without altered food intake	[1]
Diet combination	Obese mice switched to lean diet	Greater fat-mass loss and normalised liver adiposity vs. diet alone	[11]
Skeletal-muscle ageing	Aged mice, injury model	Activation of senescent satellite cells; improved regeneration	[12]
Cancer metabolism	NNMT-high cell lines; CAF proteomics	NNMT as methylation sink; stromal reprogramming	[6,13]

Adipose and whole-body metabolism

The 2018 study remains the anchor dataset. Systemic administration of the lead quinolinium inhibitor to diet-induced obese mice was associated with reduced body weight, smaller adipocytes and lower plasma cholesterol, with no reported change in food intake or overt adverse findings [1]. A 2021 study from the same group combined the inhibitor with a switch from a Western diet to a reduced-calorie diet and reported faster body-weight and fat-mass reduction, a higher lean-to-body-mass ratio and normalised hepatic steatosis relative to diet change alone; adipose tissue metabolomics showed enrichment of ketogenic amino acids [11]. No controlled human trial has been published.

Skeletal muscle and cellular senescence

In 2019 the compound was investigated in aged mice following muscle injury. NNMT inhibition was associated with activation of previously senescent muscle stem (satellite) cells and improved regenerative capacity, an effect the authors attributed to preservation of the NAD+ pool in the stem-cell niche [12]. The dataset involves a single injury model and one age cohort.

Oncology and epigenetics

NNMT is over-expressed in many solid tumours and in cancer-associated fibroblasts (CAFs), where proteomic profiling identified it as a master regulator of the stromal phenotype; genetic or pharmacological NNMT suppression in CAFs restored histone methylation and reduced tumour-supportive signalling in ovarian cancer models [6,13]. Intratumoural exposure of quinolinium inhibitors has not been established.

Limitations and open questions

• No human data. Every efficacy dataset for 5-Amino-1MQ is preclinical [1,11,12]; human evidence exists only as correlational associations between NNMT expression, 1-MNA levels and insulin resistance [5].
• Tissue-context paradox. Hepatic NNMT appears protective through SIRT1 stabilisation [8], so systemic inhibition may have divergent effects across organs.
• Permanent cation pharmacology. Quaternary ammonium compounds often show low oral bioavailability; the 2018 study used parenteral delivery in mice, and pharmacokinetic characterisation remains sparse [1].
• Identity verification. Because the compound is not a peptide, standard peptide-purity workflows (peptide-mapping MS) do not apply; HPLC-UV with reference standard and ¹H-NMR are the appropriate identity tests for a quinolinium salt.

Where to source for research

5-Amino-1MQ is listed by several research-chemical suppliers, typically as a lyophilised powder in vials labelled by milligram content. Researchers evaluating suppliers should request a lot-specific certificate of analysis showing HPLC purity and mass confirmation for the quinolinium cation. Current research-grade availability includes Short Chain Aminos, BioPep, Catalyst Research and Apex Research Services. Our supplier evaluation guide and supplier reviews outline the documentation researchers can reasonably expect. All listings are for laboratory research use only.

Frequently asked questions

what is 5 amino 1mq

5-Amino-1MQ is 5-amino-1-methylquinolinium, a small-molecule, cell-permeable inhibitor of nicotinamide N-methyltransferase (NNMT). It was identified in a 2017 medicinal-chemistry screen of quinolinium analogues and characterised in 2018 as a nicotinamide-competitive inhibitor with roughly micromolar potency [1,2]. It is a quaternary ammonium salt, not a peptide.

what does 5 amino 1mq do

In cell and mouse studies, 5-Amino-1MQ has been reported to inhibit NNMT, lowering 1-methylnicotinamide output while raising intracellular NAD+ and SAM [1]. Downstream observations in mice include reduced adipose mass and improved muscle regeneration after injury [1,12]. These are preclinical findings; no human efficacy data have been published.

Is 5-amino-1mq a peptide?

No. A peptide is a chain of amino acids joined by amide bonds. 5-Amino-1MQ is a bicyclic aromatic cation of about 159 g/mol with a single primary amine and no amide backbone. The strings "5 amino peptide" and "5-amino peptide" are catalogue conventions arising from its placement in peptide supplier listings [2].

How does 5-Amino-1MQ differ from JBSNF-000088 and NS1?

All three inhibit NNMT but by different modes. 5-Amino-1MQ is a competitive quinolinium cation binding the nicotinamide site [2]; JBSNF-000088 is a slow-turnover substrate analogue that is itself methylated [9]; NS1 is a bisubstrate conjugate spanning both the nicotinamide and SAM pockets with sub-nanomolar affinity but limited cell permeability [10].

Why are there so many spellings, such as 5amino1mq or 5-amino-1q?

The name combines a locant prefix, a position number and an abbreviation, which invites dropped hyphens ("5amino 1mq"), dropped letters ("5-amino-1q") and dropped segments ("5-amino"). All of these refer to the same 5-amino-1-methylquinolinium cation; none denotes a different compound.

What does a "5-amino-1mq 50mg" listing mean?

It describes the mass of lyophilised material supplied in a research vial. Vial mass is a catalogue attribute used for inventory and analytical planning; it carries no information about experimental protocols, and this article provides none.

Is NNMT inhibition the same as NAD+ supplementation?

No. NAD+ precursors add substrate to the salvage pathway, whereas NNMT inhibition is hypothesised to spare nicotinamide from methylation and simultaneously preserve SAM [1,5]. The two approaches act on different nodes and have been studied separately; see the site's NAD+ review.

Works Cited

1. Neelakantan H, Vance V, Wetzel MD, et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141–152. doi:10.1016/j.bcp.2017.11.007. PMID 29155147.
2. Neelakantan H, Wang HY, Vance V, et al. Structure–activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60(12):5015–5028. doi:10.1021/acs.jmedchem.7b00389. PMID 28548833.
3. Aksoy S, Szumlanski CL, Weinshilboum RM. Human liver nicotinamide N-methyltransferase: cDNA cloning, expression, and biochemical characterization. J Biol Chem. 1994;269(20):14835–14840. PMID 8182091.
4. Peng Y, Sartini D, Pozzi V, et al. Structural basis of substrate recognition in human nicotinamide N-methyltransferase. Biochemistry. 2011;50(36):7800–7808. doi:10.1021/bi2007614. PMID 21823666.
5. Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends Endocrinol Metab. 2017;28(5):340–353. doi:10.1016/j.tem.2017.02.004. PMC5446048.
6. Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat Chem Biol. 2013;9(5):300–306. doi:10.1038/nchembio.1204. PMID 23455543.
7. Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258–262. doi:10.1038/nature13198. PMID 24717514.
8. Hong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21(8):887–894. doi:10.1038/nm.3882. PMID 26168293.
9. Kannt A, Rajagopal S, Kadnur SV, et al. A small molecule inhibitor of nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018;8:3660. doi:10.1038/s41598-018-22081-7. PMID 29483571.
10. Policarpo RL, Decultot L, May E, et al. High-affinity alkynyl bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT). J Med Chem. 2019;62(21):9837–9873. doi:10.1021/acs.jmedchem.9b01238. PMID 31589440.
11. Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Sci Rep. 2021;11:5637. doi:10.1038/s41598-021-85051-6. PMC7952898.
12. Neelakantan H, Brightwell CR, Graber TG, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019;163:481–492. doi:10.1016/j.bcp.2019.02.008. PMC6469996.
13. Eckert MA, Coscia F, Chryplewicz A, et al. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature. 2019;569(7758):723–728. doi:10.1038/s41586-019-1173-8. PMID 31043742.

All content strictly for research reference. 5-Amino-1MQ and the other NNMT inhibitors discussed are research chemicals; they are not for human or veterinary use, and nothing in this article constitutes guidance on handling, administration or protocols. Related reviews: 5-Amino-1MQ single-compound review · NAD+ · MOTS-c · SLU-PP-332 and the ERR agonist family.