What is 5-amino-1MQ?

Drop the fat and access the fountain of youth in one peptide? Is that to good to be true? The answer is, NO! It is possible and it’s called 5-amino-1MQ. 5-amino-1MQ is a small molecule drug that functions to block the activity of an enzyme called nicotinamide N-methyltransferase (NNMT). Given its a primary metabolizing function, NNMT is predominantly expressed in the liver, but significant levels of the enzyme are also present in other tissues including adipose tissue, kidney, brain, lung, heart, and muscle. Enhanced activity of NNMT has been linked to a number of chronic diseases including cancer development. NNMT expression has also been reported to be upregulated in patients with Parkinson’s disease and suggested to be linked to the production of neurotoxins such as N-methylpyridinium ions that underlie neurodegeneration.

  5-amino-1MQ induces the production of NAD+ on an intracellular level. Higher NNMT have been associated with obesity and type 2 diabetes. 5-amino-1MQ is a peptide that is targeted reduction in white adipose tissue, leading to significant weight loss and improvements in obesity-linked commodities. Patients that have taken 5-amino-1MQ have experienced a decrease in weight gain, reduce fat mass, and increases energy. There was also a 30% decrease in cholesterol levels and improved cognitive function. If you’re looking to shrink fat cells and increase production of NAD+ for health and wellness benefits as well as anti-aging this is an excellent peptide!

Clinical Studies:

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

Conclusion: The current study provides conclusive evidence for the use of small molecule, “drug-like” NNMT inhibitors as a viable therapeutic approach to manage diet-induced obesity and related metabolic comorbidities. Our novel NNMT inhibitors display excellent physical chemical properties (e.g., membrane permeability), selectivity, and cellular inhibitory activity against NNMT, concomitantly enhancing the levels of the cofactors SAM and NAD+ that independently regulate cellular energy metabolism and epigenetic modifications. Importantly, treatment of DIO mice with our NNMT inhibitors did not impact food intake, but produced marked reductions in body weight, WAT mass, adipocyte size, and cholesterol levels with negligible toxicity or observable adverse effects. Future studies will be focused on optimizing the MQ-scaffold lead series to generate more potent NNMT inhibitors with significantly improved “drug-like” ADME profile. Orally bioavailable lead candidates will be tested in a comprehensive dose ranging study to confirm efficacy on obesity and co-morbid endpoints.

Full Study to Human Clinical Trial Listed Above

Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochemical Pharmacology. 2018;147(Supplement C):141-52.

Neelakantan H, Vance V, Wetzel MD, Wang H-YL, McHardy SF, Finnerty CC, et al. 

Conclusion:  Mice were subjected to experimentally-induced obesity through a high-fat diet, and were given either 20 mg/kg of 5-amino 1MQ or a sham treatment as controls every day for 11 days. The animals who received 5-amino 1MQ exhibited a significant reduction in body weight compared to the controls. This was associated with the treatment, and also with the duration of treatment. In addition, the control mice gained weight over the treatment period, whereas the mice given 5-amino 1MQ lost weight.

However, the actual food intake of the two groups over the study period was not significantly different. The mice in the “5-amino 1MQ” group also exhibited a 35% decrease in their white adipose mass, which was also a significant decrease compared to the control mice. This tissue was also found to have significant reductions in the size and volume of their white adipocytes, which may be indicative of obesity in reverse.

Furthermore, the mice in the treatment group had cholesterol levels that were approximately 30 percent lower than those of the control mice (this was also a significant difference). The blood lipid profiles of the treated mice were also similar to normal, non-obese mice of the same laboratory strain. The researchers also reported that 5-amino 1MQ reduced lipogenesis (or the formation of ‘storable’ fat) in adipocytes isolated from treated mice by up to 70%, compared to control cells. Finally, the team of researchers, who published their findings in the journal Biochemical Pharmacology, also claimed that their new drug did not appear to cause any adverse side-effects in the treated animals.