5-Amino-1MQ
5-amino-1-methylquinolinium iodide, a small-molecule NNMT inhibitor and not a peptide, as crystalline powder in a sealed vial. Every lot is tested in the manufacturer’s own laboratory with a lot certificate.
| Compound | 5-Amino-1MQ 5-Amino-1-methylquinolinium iodide (NNMT inhibitor); small molecule, not a peptide |
|---|---|
| CAS number | 42464-96-0 |
| Molecular formula | C10H11IN2 |
| Theoretical mass | 286.1 Da |
| Sequence / structure | Quinolinium salt (iodide); the 5-amino-1-methylquinolinium cation is 159.2 Da and is the species observed by ESI-MS. |
| Form | Lyophilized (freeze-dried) powder or cake in a sealed glass vial with a rubber stopper and aluminium crimp cap |
| Storage, sealed | −20 °C, desiccated, dark |
| Purity specification | 99.0% or higher by RP-HPLC |
| Format | Lyophilized powder, sealed vial |
Sizes and lots
- 5 mg · 1 vial — $60.63 · lot PL-2609-001, certificate PL-26-00001
- 5 mg · Kit of 10 — $539.00 · lot PL-2609-001, certificate PL-26-00001
- 50 mg · 1 vial — $122.25 · lot PL-2609-002, certificate PL-26-00002
- 50 mg · Kit of 10 — $1086.80 · lot PL-2609-002, certificate PL-26-00002
5-amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase, or NNMT, and it is not a peptide, although it is often listed with them. This is the main 5-amino-1MQ vial: 50 mg of the iodide salt as a brownish-orange crystalline powder, with a 5 mg vial also sold. The research behind it is preclinical, centred on one university group's chemistry and mouse work on NNMT, fat cell metabolism and diet-induced obesity.
The iodide salt and the mass on the label
The certificate names the compound as 5-amino-1-methylquinolinium iodide, C10H11IN2, with a theoretical mass of 286.1 Da, and the 50 mg on the label is that salt. The part that acts on NNMT is the cation, which weighs 159.2 Da and carries a permanent positive charge on its ring nitrogen. Electrospray mass spectrometry sees the cation, not the salt, so the certificate reports the LC-MS identity as the [M]+ ion near 159 Da. A value there is the expected result, not a mismatch with the 286.1 Da formula weight.
In molar terms 50 mg of the salt is about 175 µmol, and since each formula unit carries one cation, that is also the amount of the active ion. By mass, a little over half the fill is cation and the rest is iodide. The residual water the certificate reports lowers these figures slightly. The same salt is sold as a 5-amino-1MQ 5 mg vial, as 5-amino-1MQ capsules and in solution in a 5-amino-1MQ preloaded pen.
Handling notes
Unlike most compounds in the catalogue, 5-amino-1MQ carries GHS hazard classifications. The safety data sheet lists it as harmful if swallowed (H302), a skin irritant (H315), a serious eye irritant (H319) and a possible cause of respiratory irritation (H335), and asks for it to be stored locked up. Its sections on protective equipment and first aid apply whenever the vial is opened. The certificate gives storage as −20 °C, desiccated and dark. Let the sealed vial reach room temperature before opening so condensation does not form on the solid, and keep solutions at 2 to 8 °C, protected from light, for no longer than your laboratory has established.
What the research covers
The enzyme: NNMT
Nicotinamide N-methyltransferase is a cytosolic enzyme that moves a methyl group from S-adenosylmethionine (SAM) onto nicotinamide, producing 1-methylnicotinamide (MNA)1. It was first known as the enzyme that marks surplus vitamin B3 for excretion, and Pissios reviewed the later evidence that it shapes metabolic pathways in fat, liver and cancer cells by consuming methyl donors and producing active metabolites2. Much of the metabolic interest dates from 2014, when Kraus and colleagues found NNMT expression raised in the white fat and liver of obese and diabetic mice3. Knocking the enzyme down in those tissues protected the mice from diet-induced obesity by increasing cellular energy expenditure, and NNMT inhibition raised SAM and NAD+ in fat tissue3.
Where 5-amino-1MQ came from
5-amino-1MQ belongs to a series of methylated quinolinium compounds developed by Neelakantan, Watowich and colleagues at the University of Texas Medical Branch4. Their 2017 structure-activity study screened N-methylated quinolinium, isoquinolinium, pyridinium, benzimidazolium and benzothiazolium analogues and picked out the quinoliniums as the most promising scaffold, with inhibition in the low micromolar range (IC50 around 1 µM)4. Docking the inhibitors into the nicotinamide-binding site gave scores that tracked the measured IC50 values4. The 2018 follow-up tested permeability, selectivity and effects in cells and mice5. Quinoliniums with a primary amine substituent crossed membranes well in artificial-membrane and Caco-2 assays, by both passive and active transport, and they did not inhibit related SAM-dependent methyltransferases5. In cultured adipocytes the inhibitors lowered MNA, raised NAD+ and SAM, and suppressed lipogenesis5. The paper's title reports that they reversed high-fat-diet-induced obesity in mice; over the 11-day study, body weight and white fat mass fell while food intake did not change5.
Other inhibitors of the same enzyme
Work with structurally different inhibitors supports NNMT as the target without testing 5-amino-1MQ itself. Kannt and colleagues described JBSNF-000088, a nicotinamide analogue that reduced MNA levels, lowered body weight, improved insulin sensitivity and normalised glucose tolerance in mice with diet-induced obesity1. The effects were absent in NNMT knockout mice on the same diet, which the authors took as evidence of specificity1. A co-crystal structure showed the methylated product of JBSNF-000088 bound to the enzyme, so it may act as a slow-turnover substrate analogue1.
What is not established
None of the references reports any study in people: there is no clinical trial and no human pharmacokinetic or safety data. The compound-specific findings come from one laboratory, and the obesity study ran for 11 days. Kannt's group saw improved glucose handling in ob/ob and db/db mice without any weight change, so results differ between mouse models even for a single inhibitor1. Pissios also listed key gaps in what is known about NNMT itself2. The 5-amino-1MQ guide covers later studies, including work on aged muscle. None of these papers used SCALE Performance material.
Frequently asked questions
Is 5-amino-1MQ a peptide?
No. It is a small molecule, a quinolinium salt with no amino acids, and the active cation weighs only 159.2 Da. SCALE Performance lists it beside its peptides for convenience, but its chemistry and its hazards are those of a small organic salt.
How do the 50 mg and 5 mg vials differ?
Only in the amount of salt. Both hold the iodide as a crystalline powder, and each fill is made and tested as its own lot with its own certificate. The 50 mg vial suits a longer series of experiments; the 5 mg vial suits small pilot work.
How should the vial be stored and handled?
Sealed at −20 °C, dry and dark. The compound is classified as harmful if swallowed and irritating to skin, eyes and airways, so open it with the precautions on the safety data sheet. Solutions go at 2 to 8 °C, protected from light.
What does the research show, and what does it leave open?
In enzyme assays, cultured fat cells and mice made obese on a high-fat diet, the quinolinium inhibitors blocked NNMT, lowered MNA and were reported to reverse diet-induced obesity over a short study. There are no human studies of any kind, and the compound-specific work comes from one group.
References
- 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(1):3660. DOI · PubMed
- Pissios P. Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme. Trends Endocrinol Metab. 2017;28(5):340-353. DOI · PubMed
- Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258-62. DOI · PubMed
- 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 · PubMed
- 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 · PubMed
For laboratory research use only. Not for human or veterinary consumption. Products have not been evaluated by the U.S. Food and Drug Administration and are not intended to diagnose, treat, cure or prevent any disease.