5-Amino-1MQ
Category: Small molecules · Last updated
5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule selective inhibitor of nicotinamide N-methyltransferase (NNMT). It is a research compound studied for its effects on adipocyte methyl-donor consumption and the resulting downstream effects on energy expenditure, fat mass, and skeletal-muscle function.
Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / 5-Amino-1MQ](https://peppudex.com/peptides/5-amino-1mq).
Overview
NNMT consumes the universal methyl donor S-adenosyl methionine (SAM) and converts nicotinamide (a NAD+ precursor) into 1-methylnicotinamide. NNMT is overexpressed in obese adipose tissue and is correlated with metabolic dysfunction. Inhibiting NNMT spares SAM for other methylation reactions and increases the available pool of nicotinamide for NAD+ salvage.
5-Amino-1MQ was developed by the Erion group at the University of Texas Medical Branch and screened as a selective small-molecule NNMT inhibitor with reasonable oral bioavailability in animal models.
Mechanism
The compound is an active-site competitive inhibitor of NNMT. Effects observed in preclinical models:
- Reduced 1-methylnicotinamide pool in adipocytes
- Spared SAM for histone and DNA methyl-transfer reactions
- Increased NAD+ availability for sirtuin and PARP activity
- Reduced adipocyte hypertrophy in diet-induced obese mice
- Improved aged-muscle stem-cell function in murine models (Neelakantan et al., 2019)
Evidence
Preclinical evidence is limited to animal studies:
- Neelakantan et al., 2019 · 5-Amino-1MQ restores muscle-stem-cell function in aged mice (PMID 31412175)
- Kannt et al., 2018 · NNMT inhibition reduces adiposity in diet-induced obese mice (PMID 29643404)
- No human clinical trials have been registered for 5-Amino-1MQ as of 2026-05.
Dosing literature
Animal studies dose orally at 5-20 mg/kg/day. Bioavailability and human pharmacokinetics are not published. The wiki does not recommend any human dose; this is an investigational compound with preclinical data only.
Storage
Lyophilized 5-Amino-1MQ is stable at –20 °C for at least 24 months. Once dissolved (the compound is water-soluble), store at 2-8 °C and use within 14-30 days.
Regulatory status
- United States. Investigational research compound. Not FDA-approved. No completed Phase 3 trials.
- WADA. Not listed as of the 2024 Prohibited List.
See also
- NAD-plus · downstream beneficiary of NNMT inhibition
- Sirtuin_activation · NAD+-dependent deacetylase signaling
- AMPK · methylation cross-talks with energy-sensing pathways
- [Peppudex card · 5-Amino-1MQ](https://peppudex.com/peptides/5-amino-1mq) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources
References
- Neelakantan H, 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. PMID 29128375.
- Kannt A, et al. "A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders." Sci Rep. 2018;8(1):3660. PMID 29483579.
- Neelakantan H, 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. PMID 31412175.