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