What Is 5-Amino-1MQ?
Quick Answer
⚠️ Important: 5-Amino 1MQ is a small molecule (methylquinolinium derivative), not a peptide chain. It is an experimental research chemical — not FDA-registered, not GRAS, and banned by WADA (S0 category). 5-Amino 1MQ (5-amino-1-methylquinolinium, CAS 42464-96-0) is a synthetic small molecule classif...
⚠️ Important: 5-Amino 1MQ is a small molecule (methylquinolinium derivative), not a peptide chain. It is an experimental research chemical — not FDA-registered, not GRAS, and banned by WADA (S0 category).
5-Amino 1MQ (5-amino-1-methylquinolinium, CAS 42464-96-0) is a synthetic small molecule classified as a methylquinolinium derivative. [1] It was developed by Dr. Stanley J. Watowich’s research group at the University of Texas Medical Branch (UTMB) at Galveston as a selective inhibitor of the metabolic enzyme nicotinamide N-methyltransferase (NNMT). [2]
5-Amino 1MQ is an analogue of the parent molecule 1-methylquinolinium (1-MQ), modified with a primary amine substitution at the 5-position of the quinoline ring. This structural modification was rationally designed to optimize binding affinity to NNMT while dramatically improving membrane permeability — a critical limitation of the parent 1-MQ molecule. [3]
In conditions such as obesity, type 2 diabetes, and aging, NNMT is overexpressed in adipose tissue and skeletal muscle, where it depletes cellular pools of NAD+ and SAM. By blocking NNMT, 5-Amino 1MQ preserves these critical metabolic cofactors, shifting cellular metabolism from fat storage to fat oxidation and energy expenditure. [4]
Regulatory Status:
- FDA: NOT registered for human use — experimental research chemical. [5]
- WADA: Banned under S0 category (Non-Approved Substances) — prohibited at all times.
- GRAS: Not classified as Generally Recognized as Well-tolerated for dietary supplementation.
Developer: Ridgeline Therapeutics (Houston, TX), founded by Dr. Watowich, is advancing a lead NNMT inhibitor candidate (RT-002) toward Phase 1 first-in-human clinical trials, with IND-enabling GLP toxicology studies in minipigs currently underway. [6]
Pharmacokinetic Highlights:
- Oral Bioavailability: 38.4% (rats) [7]
- Half-Life: ~6.9 hours (oral), ~3.8 hours (IV) in rats
- Cmax: 2,252 ng/mL (oral, rats)
- Membrane Permeability: High (passive and active transport)
References
- Neelakantan H, Wang HY, Vance V, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015–5028, 2017.
- Neelakantan H, Brightwell CR, Graber TG, et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol, 147, 141–152, 2018.
- Neelakantan H, Vance V, Wetzel MD, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015-5028, 2017.
- Sun WD, Zhu GY, Li J, et al. Nicotinamide N-methyltransferase (NNMT): a novel experimental target for metabolic syndrome. Front Pharmacol, 15, 1410479, 2024.
- World Anti-Doping Agency (WADA). The World Anti-Doping Code International Standard: Prohibited List 2025. S0: Non-Approved Substances.
- Watowich SJ. SBIR Award: NNMT Inhibitor Development. National Institute on Aging (NIA), 2021.
- Awosemo O, Neelakantan H, Watowich SJ, et al. Development & Validation of LC–MS/MS Assay for 5-Amino-1-Methyl Quinolinium in Rat Plasma. J Pharm Biomed Anal, 204, 114255, 2021.
- Liu JR, Deng ZH, Zhu XJ, et al. Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes. BioMed Res Int, 2021, 9924314, 2021.
- Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition in obese mice. Sci Rep, 11(1), 5637, 2021.
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Sci Rep, 14(1), 15554, 2024.
- Neelakantan H, Vance V, Wang HYL, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol, 163, 481–492, 2019.
- Babula J, Dimet-Wiley AL, Seyoum B, et al. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab, 26(11), 5272–5282, 2024.
- Li XY, Pi YN, Chen Y, et al. Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy. Front Oncol, 12, 894744, 2022.
- Moody TW, Nuche-Berenguer B, Jensen RT. Cancer and NNMT overexpression in aggressive tumors. Curr Opin Endocrinol Diabetes Obes, 2022.
- Dimet-Wiley A, Sampson CM, Neelakantan H, et al. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep, 12(1), 484, 2022.
- Dong G, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease. Acta Physiol, 2025.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 12,071,409, August 27, 2024.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 11,401,243, August 2, 2022.
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