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Metabolic Modulators

5-Amino-1MQ

Oral NNMT inhibitor that raised NAD+ and shrank fat cells in obese mice; promising mechanism but no human studies.

RestrictedEvidence level 2 of 5: Animal data, minimal humanAlso: 5-Amino-1-methylquinolinium, 5-amino-1-methylquinolinium iodide, NNMT inhibitor 5A1MQ

Overview

5-Amino-1MQ is a small molecule, not a peptide, that blocks nicotinamide N-methyltransferase (NNMT), an enzyme that is overactive in the fat tissue of people with obesity. NNMT consumes nicotinamide and methyl groups; blocking it raises cellular NAD+ and SAM and shifts fat cells toward burning rather than storing energy. In obese mice, it reduced weight and fat mass without suppressing appetite, and in aged mice it improved muscle stem-cell activity. No human trials have been published, so dose, safety and benefit in people are unknown. Because NNMT inhibition alters methyl-group balance, homocysteine and B-vitamin status are monitored.

Classification
Small-molecule NNMT (nicotinamide N-methyltransferase) inhibitor; not a peptide
Route
Oral
Half-life
Not well established

Mechanism of action

Primary targetNicotinamide N-methyltransferase (NNMT)
  1. Enters adipocytesSmall, membrane-permeable molecule reaches fat and muscle cells.
  2. Inhibits NNMTBlocks methylation of nicotinamide using SAM as a methyl donor.
  3. NAD+ and SAM riseSpared nicotinamide recycles to NAD+; SAM pool is preserved.
  4. Sirtuin and energy activationHigher NAD+ supports SIRT1 activity and mitochondrial metabolism.
  5. Reduced fat storageAdipocytes shift from lipogenesis toward energy expenditure.
Downstream effects
  • Reduced fat mass (mice)
  • Higher cellular NAD+
  • Muscle stem-cell support (mice)

Researched for

  • Obesity (preclinical)
  • Age-related muscle decline (preclinical)
  • Type 2 diabetes and insulin resistance
  • NAD+ metabolism

Research notes

  • Diet-induced obese mice (Neelakantan 2018): reduced weight, white fat mass and adipocyte size; food intake unchanged.
  • Aged mice (Neelakantan 2019): improved muscle stem-cell function and muscle regeneration after injury.
  • No human pharmacokinetic, efficacy or safety data have been published.
  • Commercial products are research chemicals; purity and dose accuracy are unverified.

Reported side effects

  • Limited data — long-term effects unknown
  • Possible rise in homocysteine
  • Mild GI upset (anecdotal)
  • Headache (anecdotal)

Contraindications & cautions

  • Pregnancy or breastfeeding
  • Active malignancy (NAD+ effects in cancer unclear)
  • Hyperhomocysteinemia or methylation disorders
  • Significant liver or kidney disease

Lab monitoring

  • Homocysteine
  • Vitamin B12 and folate
  • Fasting glucose, HbA1c, fasting insulin
  • Lipid panel
  • CMP

Dosing and pricing for 5-Amino-1MQ

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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