5-Amino-1MQ

5-Amino-1MQ

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Small molecule NNMT inhibitor (not a traditional peptide) that restores cellular NAD+ levels, enhances fat oxidation, and suppresses lipogenesis by blocking nicotinamide N-methyltransferase.

Quick Facts

Property Value
Also Known As 5-A1MQ, 5-Amino-1-Methylquinolinium, 5-Amino-1MQ
Category Metabolic / Weight Loss / NAD+ Restoration
Sequence N/A (small molecule quinolinium compound, not a peptide)
Molecular Weight ~173.2 Da
Molecular Formula C10H10N2O
PubChem CID 134464795
Administration Oral (38.4% oral bioavailability) / SubQ
Typical Dose Range 50-150 mg/day oral (from literature)
Half-Life Not fully characterized in humans; preclinical data suggest moderate oral half-life
Storage Room temperature; protect from humidity and light. Stable in cool, dry conditions.
FDA Status Research only. No IND filed. No human clinical trials published.
WADA Status Prohibited (S0 – Non-Approved Substances)

Mechanism of Action

5-Amino-1MQ is a potent, cell-permeable inhibitor of nicotinamide N-methyltransferase (NNMT), with an IC50 of approximately 1.2 micromolar. NNMT is a cytosolic enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). By blocking this reaction, 5-Amino-1MQ simultaneously preserves two critical metabolic cofactors: NAD+ precursors (nicotinamide) and SAM, the universal methyl donor (PMID 29155147).

The downstream metabolic consequences are substantial. Increased intracellular NAD+ activates the sirtuin family of deacetylases (SIRT1, SIRT3), which orchestrate metabolic reprogramming toward fat oxidation, mitochondrial biogenesis, and improved insulin sensitivity. NNMT inhibition also reduces adipocyte differentiation and promotes a "browning" phenotype in white adipose tissue, shifting energy balance toward thermogenesis rather than storage (PMID 39161060).

In diet-induced obesity (DIO) mouse models, 5-Amino-1MQ treatment produced dose-dependent reductions in body weight, fat mass, and adipocyte size without affecting food intake or lean mass. The compound also reduced plasma total cholesterol, improved hepatic steatosis markers, and activated muscle stem cells via NNMT inhibition, suggesting anti-sarcopenic properties beyond simple weight loss (PMID 33453420).

Pharmacokinetic studies in rats have demonstrated oral bioavailability of 38.4%, supporting the viability of oral dosing as the primary administration route (PMID 34304009).

Key Research Areas

  1. Obesity and fat loss – Dose-dependent weight and fat mass reduction in DIO mice without affecting food intake or lean mass
  2. NAD+ metabolism – Restoration of cellular NAD+ pools by preserving nicotinamide from NNMT-mediated methylation
  3. Adipocyte biology – Inhibition of adipogenesis and promotion of white-to-beige fat conversion (thermogenesis)
  4. Sarcopenia prevention – Activation of senescent muscle stem cells via NNMT inhibition, supporting muscle preservation
  5. Cardiovascular protection – Emerging evidence for cardiac function improvement in HFpEF models through NNMT inhibition
  6. Metabolic syndrome – Broad metabolic improvements including cholesterol reduction, hepatic steatosis amelioration, and insulin sensitization
  7. Gut microbiome – NNMT inhibition modulates gut microbiome composition in DIO models

Evidence Level Summary

Evidence Type Count Notes
Human RCTs 0 No human trials published
Human observational 0
Animal in vivo 4 DIO mouse models, PK rat study, HFpEF mouse model, gut microbiome
In vitro 1 Adipocyte differentiation, NNMT enzymatic assays
Systematic reviews 0
Narrative reviews 5 NNMT as therapeutic target, metabolic/epigenetic crossroads, cardiovascular

Clinical Applications

  • Fat Loss — Reduces fat mass via lipolysis enhancement and lipogenesis suppression through NAD+/sirtuin pathway
  • Weight Management — Body weight reduction without lean mass loss in preclinical models
  • Sarcopenia — NNMT inhibition reactivates senescent muscle stem cells, preserving muscle during weight loss

Protocols Using This Peptide

Ageless Peps Products

  • AP-5Amino-Vial — 5-Amino-1MQ 10mg Vial, $42 (WC 759)
  • AP-5Amino-Capsules — 5-Amino-1MQ 50mg x 60 Capsules, $174 (WC 793)

Dosing Reference

Research Dosing Ranges (from literature)

Route Dose Range Frequency Duration Source
Oral 50-150 mg/day BID (split dose) 4-8 weeks on / 2-4 weeks off Practitioner consensus; animal dose translation
SubQ Dosing not well established in literature

Cycling

Recommended cycling: 4-8 weeks on / 2-4 weeks off. Conservative start at 50 mg/day for week 1, then increase to 100-150 mg/day as tolerated. Can be taken with or without food. Oral is the preferred route given demonstrated bioavailability.

Contraindications & Safety

  • Contraindications: Active malignancy (NNMT is expressed in several tumor types; role is complex and context-dependent); pregnancy/breastfeeding (no data)
  • Common side effects: Generally well tolerated in animal studies; human safety profile not established. GI discomfort possible with oral dosing.
  • Drug interactions: Theoretical interaction with NAD+ precursor supplements (NMN, NR) — may have additive effects. Theoretical interaction with PARP inhibitors or other NAD+-consuming pathways.
  • Pregnancy/nursing: No data; not recommended
  • Special populations: No human data for any special population. Preclinical only.

Synergistic Combinations

  • Semaglutide or Tirzepatide + 5-Amino-1MQ — GLP-1 appetite suppression + NNMT-mediated fat oxidation for synergistic weight loss
  • AOD-9604 + 5-Amino-1MQ — Dual lipolytic mechanism: direct adipose lipolysis + NAD+/sirtuin metabolic reprogramming
  • CJC-1295 NO DAC + Ipamorelin + 5-Amino-1MQ — GH axis body recomposition + metabolic optimization
  • NAD+ + 5-Amino-1MQ — Complementary NAD+ restoration via direct supplementation + NNMT blockade

Related Research

PMID Title Year Study Type
PMID-29155147 – 5-Amino-1MQ Reverses High Fat Diet Obesity in Mice 5-Amino-1MQ reverses high-fat diet obesity in mice 2017 Animal in vivo
PMID-39161060 – 5A1MQ Dose-Response in DIO Mice 5-Amino-1MQ dose-response in diet-induced obese mice 2024 Animal in vivo
PMID-34304009 – 5-Amino-1MQ Pharmacokinetic and Oral Bioavailability 5-Amino-1MQ pharmacokinetic and oral bioavailability study 2021 Animal PK
PMID-33453420 – Nicotinamide N-methyltransferase At the crossroads between NNMT at the crossroads between cellular metabolism and epigenetic regulation 2021 Narrative review
PMID-39604638 – Exploring NNMT from metabolic pathways to therapeutic targe Exploring NNMT from metabolic pathways to therapeutic targets 2024 Narrative review
PMID-38919254 – Nicotinamide N-methyltransferase (NNMT) a novel therapeutic NNMT: a novel therapeutic target for metabolic syndrome 2024 Narrative review
PMID-41008588 – Nicotinamide N-Methyltransferase in Cardiovascular Diseases NNMT in cardiovascular diseases: metabolic regulator and emerging target 2025 Narrative review
PMID-40484359 – Nicotinamide-N-methyltransferase inhibition improves cardiac NNMT inhibition improves cardiac function in HFpEF mouse model 2025 Animal in vivo
PMID-30753815 – NNMT Inhibitor Activates Senescent Muscle Stem Cells NNMT inhibitor activates senescent muscle stem cells 2019 Animal in vivo
PMID-35013352 – NNMT Inhibition and Gut Microbiome in DIO Mice NNMT inhibition and gut microbiome in DIO mice 2022 Animal in vivo

References

  • PMID 29155147 — Original obesity reversal study in DIO mice
  • PMID 39161060 — Dose-response characterization
  • PMID 34304009 — Pharmacokinetic and oral bioavailability data (38.4%)
  • PMID 33453420 — NNMT metabolic/epigenetic crossroads review
  • PMID 38919254 — NNMT as metabolic syndrome target
  • PMID 30753815 — Muscle stem cell activation via NNMT inhibition

Related

#peptide #metabolic #subq #oral