5-Amino-1MQ

Research summary

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the enzyme that methylates nicotinamide using S-adenosylmethionine (SAM) and so links NAD+ metabolism with the cell's methylation balance¹. It is not a peptide. The studies that name it were carried out in cultured cells and mice^2,3,4,5, and Peptides Only supplies it, as the iodide salt, for laboratory research only.

Also known as

5-Amino-1-methylquinolinium · 5-Amino-1-methylquinolinium iodide · 5A1MQ · 5-Amino 1MQ

What is 5-Amino-1MQ?

5-Amino-1MQ is a small organic molecule: a quinoline ring with an amino group at position 5 and a methyl group on the ring nitrogen, which gives it a permanent positive charge. It is supplied as the iodide salt, and papers abbreviate it as 5A1MQ or 5MQ^2,4.

It comes out of a medicinal-chemistry program on NNMT inhibitors. A 2017 structure–activity study of N-methylated quinolinium and related heterocycles identified quinoliniums as a promising scaffold, with low-micromolar NNMT inhibition and predicted binding in the enzyme's nicotinamide site⁶. A 2018 follow-up reported that methylquinolinium analogues carrying primary amine substitutions, the class 5-amino-1MQ belongs to, crossed membranes readily and did not inhibit related SAM-dependent methyltransferases or NAD+ salvage-pathway enzymes⁷. Neither abstract names individual compounds, so these are findings about the series.

What is NNMT, and why is it studied?

NNMT transfers a methyl group from SAM, the universal methyl donor, to nicotinamide, a form of vitamin B3 and an NAD+ precursor. That places it at the junction of one-carbon metabolism, the cell's methylation balance and NAD+ levels¹. Its expression is tissue-specific: in adipose tissue it correlates with obesity and insulin resistance, and it is raised in a variety of cancers¹.

In a 2014 mouse study, NNMT expression was raised in the adipose tissue and liver of obese and diabetic mice, and knocking it down in those tissues protected against diet-induced obesity by increasing energy expenditure, with higher adipose SAM and NAD+ and increased polyamine flux⁸. In people, adipose NNMT expression was about twofold higher in patients with type 2 diabetes than in controls, and plasma 1-methylnicotinamide, the product of the reaction, correlated with adipose NNMT expression in those patients⁹.

What the research on 5-Amino-1MQ has examined

In diet-induced obese (DIO) mice, Babula and colleagues compared 5A1MQ with vehicle over 28 days. Treated mice gained less body weight and fat mass, showed better oral glucose tolerance and insulin sensitivity, and had less fatty liver, including lower liver triglycerides; the compound reached high systemic exposure and distributed to adipose tissue, muscle and liver². In a separate study, DIO mice switched to a low-fat diet and given 5-amino-1-methylquinolinium returned to the adiposity and body weight of age-matched lean mice, which the diet switch alone did not achieve in the same time frame, and developed a distinct cecal microbiome³. Earlier work on the series reported that NNMT inhibitors lowered intracellular 1-methylnicotinamide, raised NAD+ and SAM and suppressed lipogenesis in cultured adipocytes, and that a potent inhibitor reduced body weight and white adipose mass in DIO mice without changing food intake⁷.

Aged muscle is a second line of work. The same research group reported that a small-molecule NNMT inhibitor increased muscle stem cell proliferation and fusion after injury in 24-month-old mice, producing larger regenerating fibers and about 70% higher peak torque than controls, and promoted differentiation of C2C12 myoblasts in culture¹⁰. In mice followed from 22 to 24 months of age, NNMT inhibitor treatment was associated with about 40% greater grip strength than in sedentary controls, an effect additive with exercise¹¹. Neither abstract names the compound.

Other groups have used 5-amino-1MQ as a tool to inhibit NNMT in cancer biology. In HeLa cervical cancer cells it reduced proliferation in a concentration- and time-dependent manner, with morphological signs of apoptosis and lower phospho-Akt and SIRT1, without apparently affecting the proliferation of HEK-293 cells⁴. In mouse models of urothelial bladder cancer, where NNMT in cancer-associated fibroblasts was linked to tumor progression, the iodide salt reduced tumor growth and enhanced the apoptotic effect of an anti-PD-L1 antibody⁵.

Limitations of the evidence

• Every study cited here that names 5-amino-1MQ used cultured cells or mice^2,3,4,5; its effects in people have not been established.
• Several key abstracts describe an NNMT inhibitor or a compound series without naming 5-amino-1MQ, so not every NNMT-inhibitor finding can be attributed to it^7,10,11.
• Most of the metabolic and muscle work comes from one research group, and in the more recent papers authors disclose founding or employment ties to Ridgeline Therapeutics^2,3,11.
• Genetic studies of NNMT do not all agree: in one, Nnmt-knockout males on a high-fat diet had improved insulin sensitivity but no improvement in glucose tolerance, and effects differed by sex and diet¹².
• Human NNMT data are correlational, drawn from adipose tissue samples and plasma 1-methylnicotinamide, and do not test an inhibitor⁹.

Working with 5-Amino-1MQ in the lab

5-Amino-1MQ is supplied as a lyophilized iodide salt. The specifications list molecular weights for both the cation and the salt; the difference matters whenever a mass is converted to a molar concentration.

Every Peptides Only lot ships from the USA with a lot-matched certificate of analysis from an independent lab, reporting HPLC purity and mass-spec identity. Certificates are published in the COA library.