Research Overview
MOTS-c vs 5-Amino-1MQ is a comparison across chemical classes. MOTS-c is a 16-residue peptide encoded in the mitochondrial 12S rRNA gene, with reported actions through the folate cycle, AICAR and AMP-activated protein kinase (AMPK) (Lee et al., 2015). 5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of NNMT, the enzyme that moves a methyl group from S-adenosylmethionine (SAM) onto nicotinamide, a precursor of NAD+ (Kraus et al., 2014).
Both appear in metabolic models: cell lines, high-fat-fed or diet-induced obese mice, and aged mice. MOTS-c also has human studies that measure the endogenous peptide, while 5-Amino-1MQ has enzyme, cell and rodent data only. Disguised Alpha supplies MOTS-c (10MG, 40MG) and 5-Amino-1MQ (10MG, 50MG) as lyophilized powder for laboratory research use only.
Structure and Class
MOTS-c is MRWQEMGYIFYPRKLR, 16 standard amino acids with a free carboxyl end: C101H152N28O22S2, about 2174.6 g/mol (PubChem CID 146675088). Under the mitochondrial genetic code its 51-base-pair reading frame gives tandem start and stop codons, so its discoverers concluded the peptide is translated in the cytoplasm (Lee et al., 2015).
5-Amino-1MQ is a quinoline ring with an amino group at position 5 and a methyl group on the ring nitrogen, which carries a permanent positive charge: C10H11N2+, 159.21 g/mol (PubChem CID 950107). The iodide salt is C10H11IN2, 286.11 g/mol (CID 66522933). In the founding structure-activity study, N-methylated quinoliniums inhibited NNMT near 1 micromolar, docked computationally into its nicotinamide-binding site (Neelakantan et al., 2017).
MOTS-c is about 13.7 times heavier than the 5-Amino-1MQ cation, so compare them in moles (see the table). The product pages list the free-peptide and cation values, which match PubChem. Confirm the salt form and measured content on the lot certificate before molar work.
Side by Side
| Attribute | MOTS-c | 5-Amino-1MQ |
|---|---|---|
| Compound class | Mitochondria-derived 16-residue peptide, encoded in the 12S rRNA gene | Small-molecule NNMT inhibitor; quinolinium cation, not a peptide |
| Identity data | MRWQEMGYIFYPRKLR; C101H152N28O22S2, 2174.6 g/mol | 5-amino-1-methylquinolinium; C10H11N2+, 159.21 g/mol |
| Amount per milligram | About 0.46 µmol (free peptide) | About 6.28 µmol (cation); 3.50 µmol (iodide salt) |
| Reported mechanism | Folate cycle inhibited, AICAR accumulates, AMPK activated | NNMT inhibited; 1-methylnicotinamide falls, SAM and NAD+ rise |
| Main models | HEK293 cells, L6 myotubes; high-fat-fed, middle-aged and old mice | 3T3-L1 and Caco-2 cells; diet-induced obese and 24-month-old mice; rats |
| Human research | Measurements of the endogenous peptide; no trial findings published | None found in PubMed |
| WADA 2026 | Named in class S4.4.1; prohibited at all times | Not named |
| Supplied form | Lyophilized powder, 10MG or 40MG | Lyophilized powder, 10MG or 50MG |
| Storage listed | -20°C as shipped; 2 to 8°C after reconstitution; protected from light | Same as MOTS-c |
Research Context: MOTS-c
The discovery paper used HEK293 cells, rat L6 myotubes and mice. MOTS-c inhibited the folate cycle and the de novo purine synthesis tethered to it; AICAR accumulated more than 20-fold in cells stably expressing the peptide, and AMPK was activated. In high-fat-fed C57BL/6 mice, seven days of the peptide raised the glucose infusion rate during insulin clamps by about 30 percent, with higher insulin-stimulated glucose disposal and unchanged hepatic glucose production, and soleus muscle from 12-month-old mice regained insulin-stimulated glucose uptake to young levels (Lee et al., 2015).
In HEK293 cells under glucose restriction, serum deprivation or oxidative stress, MOTS-c moved into the nucleus as early as 30 minutes after stress, in an AMPK-dependent way, and regulated genes carrying antioxidant response elements (Kim et al., 2018). Mice given the peptide from 23.5 months of age scored higher than controls on grip strength, stride length and a 60-second walking test (Reynolds et al., 2021).
Human research history: published human studies measure endogenous MOTS-c, and no trial giving it to people has reported findings; ClinicalTrials.gov lists one registered phase 2a study (NCT07505745) as recruiting. In 10 young men, cycling raised MOTS-c about 11.9-fold in skeletal muscle and about 1.5-fold in circulation (Reynolds et al., 2021).
In 10 lean and 10 obese individuals, plasma levels were similar, near 0.5 ng/mL (Cataldo et al., 2018). A meta-analysis of seven observational studies with 602 participants found lower circulating MOTS-c in type 2 diabetes and higher in obesity, and named varied assay methods among the reasons studies disagree (Zhou et al., 2024).
Assays disagree. A mass spectrometry method validated for doping control, with a 100 pg/mL detection limit, could not confirm the 45.9 to 218.5 ng/mL that a commercial ELISA reported in 20 healthy subjects (Knoop et al., 2019).
Research Context: 5-Amino-1MQ
The target came first: antisense knockdown of Nnmt in fat and liver of high-fat-fed mice raised adipose SAM and NAD+, histone H3 lysine 4 methylation and polyamine flux. The authors noted that adipose tissue makes NAD+ mainly through nicotinamide salvage, in which NNMT is the only enzyme that breaks nicotinamide down (Kraus et al., 2014). That study used gene knockdown, not 5-Amino-1MQ.
With the compound itself, Caco-2 monolayers showed high permeability without efflux, and at 100 to 600 micromolar, depending on the enzyme, it did not meaningfully inhibit DNMT1, PRMT3, COMT, NAMPT or SIRT1. In differentiated 3T3-L1 adipocytes it lowered the NNMT product 1-methylnicotinamide and raised NAD+ about 1.2 to 1.6 fold and SAM; in differentiating cells it reduced lipid accumulation.
In male diet-induced obese C57BL/6 mice over 11 days, body weight, epididymal white adipose tissue mass and adipocyte size were lower than in vehicle controls, plasma total cholesterol was lower, and food intake did not differ (Neelakantan et al., 2018).
A 28-day study in the same model reported better glucose tolerance and less hepatic steatosis; its authors include the founder and current or former employees of Ridgeline Therapeutics (Babula et al., 2024). In 24-month-old male mice with a barium chloride injury to the tibialis anterior, the inhibitor raised muscle stem cell proliferation and fusion, with nearly twice the myofiber cross-sectional area of controls and about 70 percent higher peak torque (Neelakantan et al., 2019).
A validated LC-MS/MS method measures the intact cation in rat plasma from 10 to 2,500 ng/mL, and rat terminal half-lives were about 4 and 7 hours for the two routes compared (Awosemo et al., 2021). Human research history: no study giving 5-Amino-1MQ to people appears in PubMed or ClinicalTrials.gov (searched October 2026), and it is not an approved drug.
Choosing Between Them for a Research Question
Signaling questions point to MOTS-c: folate and purine metabolism, AICAR, AMPK activation, nuclear translocation and antioxidant response element genes (Lee et al., 2015; Kim et al., 2018). Cells make it, so samples carry an endogenous baseline, and reported concentrations differ widely between assays; record the method used (Knoop et al., 2019).
Methylation and NAD+ supply questions point to 5-Amino-1MQ: NNMT activity, 1-methylnicotinamide, the SAM pool and NAD+ salvage (Kraus et al., 2014; Neelakantan et al., 2018). It has no natural background, and a validated LC-MS/MS assay exists for it in rat plasma (Awosemo et al., 2021).
In NNMT inhibitor vs mitochondrial peptide terms, the overlap is in readouts, not mechanism: both have glucose-handling data from high-fat-fed mice. Pair such readouts with a mechanism marker (AICAR or AMPK phosphorylation for MOTS-c, 1-methylnicotinamide or SAM for 5-Amino-1MQ) and compare on moles, not milligrams.
Handling and Storage
Both product pages list the same storage: -20°C for the lyophilized powder as shipped, 2 to 8°C after reconstitution, protected from light, with freeze/thaw cycles avoided. Let a sealed vial reach room temperature before opening, and aliquot stock into single-use volumes.
MOTS-c has two methionines and a tryptophan that can oxidize, and the anti-doping method tracked two oxidation products (Knoop et al., 2019), so limit air and light and prepare working solutions fresh. The 5-Amino-1MQ product page notes that a red or reddish powder is normal for it. For molar work, use the salt form and measured content on the lot certificate in the COA portal.
Questions Researchers Ask
MOTS-c vs 5-Amino-1MQ: what is the main difference?
Class and target. MOTS-c is a 16-residue peptide encoded in mitochondrial DNA that acts through the folate cycle, AICAR and AMPK (Lee et al., 2015). 5-Amino-1MQ is a small-molecule quinolinium that inhibits NNMT; in adipocytes it raised NAD+ and SAM (Neelakantan et al., 2018).
5-Amino-1MQ vs MOTS-c: is either one a peptide?
Only MOTS-c. 5-Amino-1MQ has no amino acids or peptide bonds; the "amino" in its name is the NH2 group at position 5 of the quinoline ring. Its cation weighs 159.21 g/mol, against about 2174.6 g/mol for MOTS-c.
Have MOTS-c and 5-Amino-1MQ been studied together?
Not in any study indexed in PubMed as of October 2026. They act at different points: MOTS-c raised AICAR and activated AMPK in cells (Lee et al., 2015), while 5-Amino-1MQ lowered 1-methylnicotinamide and raised SAM and NAD+ in adipocytes (Neelakantan et al., 2018).
Are MOTS-c and 5-Amino-1MQ on the WADA Prohibited List?
MOTS-c is: the 2026 WADA Prohibited List names it in class S4.4.1, among its examples of AMPK activators, prohibited at all times. 5-Amino-1MQ is not named, but WADA notes that most classes list examples only and that class S0 covers substances not addressed elsewhere on the list that have no current approval by any government health authority for human therapeutic use.
MOTS-c and 5-Amino-1MQ are supplied strictly for laboratory and in-vitro research use. They are not for human consumption, veterinary use, or any diagnostic or therapeutic application. Nothing on this page is guidance for use in people.