MOTS-C 40mg + SS-31 50mg Bundle
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Research Use Only
These products are for laboratory research only and not intended for medical use. They are not FDA-approved to diagnose, treat, cure, or prevent any disease. By purchasing, you certify they will be used solely for research and not for human or animal consumption.
Bundle / Blend Research
This product contains MOTS-C. Select a tab below to view the full Gold Standard research profile for each component.
Overview
Overview
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid bioactive peptide belonging to the class of mitochondrial-derived peptides (MDPs).[1]
Unique origin: Unlike virtually all other bioactive peptides encoded by the nuclear genome, MOTS-c is encoded within the mitochondrial genome (mtDNA) — specifically by a short open reading frame (sORF) within the mitochondrial 12S rRNA gene (MT-RNR1). Despite being mtDNA-encoded, MOTS-c is translated in the cytoplasm using the standard genetic code (the mitochondrial code would yield tandem start/stop codons).[1][6]
MOTS-c functions as a mitokine — a mitochondrial hormone that can translocate from the mitochondria/cytoplasm to the nucleus under metabolic stress, where it binds chromatin at Antioxidant Response Elements (ARE) via the Nrf2 transcription factor, regulating approximately 1,000 genes.[3]
Structurally, MOTS-c is a linear, α-helical, amphipathic and cationic peptide (MW 2174.62 Da) with a hydrophobic core (⁸YIFY¹¹) and a cationic tail (¹³RKLR¹⁶). A naturally occurring polymorphism (K14Q, m.1382A>C) in the cationic tail has been associated with exceptional longevity in Japanese populations but reduces CK2 binding affinity.[7]
MOTS-c differs from Humanin — another MDP encoded by the 16S rRNA region — in that MOTS-c uniquely targets the folate cycle and nuclear gene expression.[6]
Mechanism of Action
Mechanism of Action
Primary Pathway: Folate → AICAR → AMPK ("Master Metabolic Switch")
MOTS-c inhibits the folate cycle at 5-methyltetrahydrofolate (5Me-THF), blocking de novo purine biosynthesis. This leads to accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), which mimics AMP and directly activates AMPK.[1]
- MOTS-c → inhibits folate cycle (5Me-THF)
- Blocked purine synthesis → AICAR accumulation
- AICAR (AMP mimetic) → direct AMPK activation
- AMPK → ACC phosphorylation → fatty acid oxidation
- AMPK → GLUT4 translocation → enhanced glucose uptake
Direct Binding Partners
| Target | Binding Domain | Functional Consequence |
|---|---|---|
| CK2α | Cationic tail (¹³RKLR¹⁶) | Skeletal muscle insulin sensitization; K14Q polymorphism reduces this binding[7] |
| Raptor (mTORC1) | Hydrophobic core (⁸YIFY¹¹) | Allosteric mTORC1 inhibition → shifts T-cell differentiation from Th1 to FOXP3+ Tregs[8] |
| Nrf2 (nuclear) | Direct chromatin binding | Nuclear translocation under stress → ARE → antioxidant gene expression (~1,000 genes)[3] |
Nuclear Translocation
Under metabolic stress (glucose restriction, oxidative stress), MOTS-c translocates from mitochondria/cytoplasm to the nucleus. It lacks a canonical nuclear localization signal (NLS) — instead relying on its hydrophobic core for entry. Once nuclear, it binds chromatin at ARE via Nrf2 transcription factor to regulate antioxidant gene expression.[3]
SIRT1/PGC-1α Pathway
MOTS-c increases intracellular NAD+ → activates SIRT1 → PGC-1α deacetylation → mitochondrial biogenesis and anti-inflammatory cytokine regulation.[6]
MAPK/ERK (Tissue-Dependent)
- Adipose tissue: Activates ERK → UCP1/PGC-1α → thermogenesis/browning of white fat[9]
- Inflammation: Inhibits ERK/JNK/p38 → suppresses NF-κB[10]
TGF-β/SMAD (Bone)
In osteoblasts: upregulates TGF-β1/2 and SMAD7 → Type I collagen synthesis → osteogenic differentiation.[11]
vs. Related Compounds
| Compound | Origin | Key Difference |
|---|---|---|
| MOTS-c | mtDNA 12S rRNA (MT-RNR1) | Targets folate cycle, nuclear translocation, exercise mimetic |
| Humanin | mtDNA 16S rRNA | Cytoprotective but does not target folate or nuclear gene expression |
| CB4211 (analog) | Synthetic (CohBar) | Engineered for improved stability/longer half-life; Phase 1b completed |
Research Applications
Research Applications
MOTS-c research spans metabolic disease, aging, exercise physiology, immunology, and bone health across 10+ indication categories:
- Metabolic Disorders (Obesity/Diabetes) — Prevents HFD-induced obesity (body weight comparable to lean controls); reverses age/diet-induced insulin resistance; effective in T1D, T2D, and gestational diabetes models.[1][8]
- Exercise Physiology — 22-month-old mice ran 2-fold longer (p=0.000002); skeletal muscle MOTS-c increased 11.9-fold during exercise in humans (n=10).[2]
- Aging & Longevity — Endogenous levels decline with age; K14Q polymorphism associated with Japanese centenarian longevity; late-life treatment → median lifespan +6.4%.[2][7]
- Cardiovascular Health — 55% reduction in vascular calcium content; 8% decrease in LV wall thickness in diabetic cardiomyopathy; prevention of heart failure.[12][13]
- Bone Metabolism — Promotes osteoblast differentiation; inhibits osteoclastogenesis via RANKL suppression; significant BMD improvements in OVX osteoporosis model.[11]
- Immunomodulation — MRSA sepsis survival 20% → 79% (pre-treatment); 50% → 100% (post-treatment); T-cell regulation (Treg vs Th1).[10]
- Pain Management — Inflammatory and bone cancer pain via AMPK → MAPK-c-fos inhibition in spinal cord.[14]
- Neuroprotection — Memory restoration via cell-penetrating analogs in Alzheimer's model; native MOTS-c does NOT cross BBB.[6]
- Cold Adaptation — BAT thermogenesis via ERK → UCP1; maintained higher body temperature during acute cold exposure.[9]
- Post-Menopausal Support — OVX mice: prevented weight gain, insulin resistance, and BAT whitening.[8]
- Cancer — Ovarian cancer suppression via LARS1 ubiquitination; conflicting data on breast/prostate risk.[6]
Biochemical Characteristics
| Property | Value |
|---|---|
| Molecular Formula | C₁₀₁H₁₅₂N₂₈O₂₂S₂ |
| Molecular Weight | 2174.62 Da |
| CAS Number | 1627580-64-6 |
| PubChem CID | 146675088 |
| Sequence (1-Letter) | MRWQEMGYIFYPRKLR |
| Sequence (3-Letter) | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Structure | Linear, α-helical, amphipathic, cationic; hydrophobic core ⁸YIFY¹¹, cationic tail ¹³RKLR¹⁶ |
| InChI Key | WYTHCOXVWRKRAH-LOKRTKBUSA-N |
| Gene Origin | MT-RNR1 (mitochondrial 12S rRNA) — mtDNA-encoded, cytoplasm-translated |
| Classification | Mitochondrial-Derived Peptide (MDP) / Mitokine |
| Key Polymorphism | K14Q (m.1382A>C) — alters cationic tail, reduces CK2 binding |
| Plasma Half-Life | ~1–2 hours (returns to baseline by 4h post-exercise) |
Identifiers
| Purity Standard | |
|---|---|
| Identity Confirmation | |
| Counter-Ion | |
| Detection Methods |
Preclinical Research Summary
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Lee et al. (2015) | CD-1/C57BL/6 mice HFD — 0.5 mg/kg/day IP × 8 wk | Prevented HFD-induced obesity (p<0.01); ~30% ↑ glucose infusion rate in clamp; 5 mg/kg × 7d reversed age-dependent insulin resistance | [1] |
| Reynolds et al. (2021) | 22-mo C57BL/6N mice — 15 mg/kg/day IP | Ran 2-fold longer (p=0.000002), 2.16× farther; 100% reached final sprint at 15 mg/kg (vs 16.6% control); late-life → +6.4% median lifespan | [2] |
| Kong et al. (2021) | NOD mice (T1D) — 0.5 mg/kg/day IP from 7 wk | 0% incidence at 19 wk vs 100% control; blood glucose 251±140 vs 547±90 mg/dL; Treg promotion via mTORC1 inhibition | [8] |
| Zhai et al. (2017) | MRSA sepsis mice — 20/50 mg/kg | Pre-treatment: survival 20% → 79%; post-treatment: 50% → 100%; ↓TNF-α/IL-6/IL-1β, ↑IL-10 | [10] |
| Wei et al. (2020) | Vascular calcification rats — 5 mg/kg/day IP × 4 wk | 55% reduction in calcium content; reduced blood pressure and stiffness via AMPK → AT-1/ET-B suppression | [12] |
| Ming et al. (2016) | OVX osteoporosis mice — 5 mg/kg/day IP × 12 wk | Significant improvements in BMD, BV/TV, trabecular thickness via AMPK → osteoclast inhibition | [11] |
| Kim et al. (2018) | C57BL/6 mice — glucose restriction | Nuclear translocation confirmed; chromatin binding at ARE via Nrf2; regulates ~1,000 genes | [3] |
| Pham et al. (2025) | T2D Wistar rats — 15 mg/kg/day IP × 3 wk | 8% ↓ LV wall thickness; restored mitochondrial respiration in diabetic hearts | [13] |
| Kong et al. (2025) | S961-treated C57BL/6 mice — 0.5 mg/kg/day | Diabetes incidence 30% vs 70% control; reduced β-gal+ cells and SASP genes | [15] |
Human Data: CB4211 (MOTS-c Analog) — NCT03998514
| Phase | Population | Intervention | Key Results | Ref |
|---|---|---|---|---|
| Phase 1a | n=65 healthy adults | 0.2–3.0 mg/kg/day SC (SAD/MAD) | Well-tolerated; mild injection site reactions only AE >10% | [4] |
| Phase 1b | n=20 obese + NAFLD (≥10% liver fat) | 25 mg/day SC × 4 weeks | ALT -21% (vs +4% placebo, p<0.05); AST -28% (vs -11%, p<0.05); fasting glucose -6% (vs 0%, p<0.05) | [4] |
Note: No completed interventional trials with native MOTS-c. CB4211 met safety endpoint; CohBar dissolved, development discontinued.
Observational Human MOTS-c Data
| Study | Population | Key Finding | Ref |
|---|---|---|---|
| Reynolds et al. (2021) | n=10 sedentary males | Skeletal muscle MOTS-c ↑11.9-fold post-exercise; plasma 1.6× during exercise, baseline by 4h | [2] |
| Yoon et al. (2026) | n=32 obese vs 22 lean | MOTS-c higher in obese (273±56 vs 223±50 pg/mL); unchanged 6mo post-bariatric surgery | [16] |
| Du et al. (2018) | n=40 obese children vs 57 controls | MOTS-c ↓ in obese males (472.61 vs 561.64 ng/mL); negatively correlated with BMI/HOMA-IR | [6] |
| Qin et al. (2017) | n=40 coronary angiography | Significantly lower MOTS-c in coronary endothelial dysfunction (p=0.007) | [6] |
Safety Summary
| Parameter | Finding |
|---|---|
| CB4211 Clinical | Well-tolerated at 25 mg/day SC × 4 wk; mild injection site reactions (persistent painless bumps) only AE >10% |
| Native MOTS-c | No established human safety data; FDA Category 2 (immunogenicity/impurity risks) |
| Anecdotal | Heart palpitations, injection site irritation, insomnia, fever, fatigue, headaches, nausea |
| Cancer Risk | Conflicting: suppresses ovarian cancer but theoretical breast/prostate risk |
| Drug Interactions | Metformin (synergistic AMPK); insulin/oral hypoglycemics (hypoglycemia risk) |
| Contraindications | WADA-banned (all sport); active malignancy (theoretical); pregnancy/breastfeeding (no data) |
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
Authors & Attribution
✍️ Article Author
Dr. Pinchas Cohen, MD
Pinchas Cohen, MD, is Dean of the USC Leonard Davis School of Gerontology and co-founder of CohBar, Inc. He led the initial discovery and characterization of MOTS-c, identifying its role in regulating metabolic homeostasis, insulin sensitivity, and preventing diet-induced obesity. His lab has overseen research into the peptide's applications for age-related diseases including diabetes, cardiovascular disease, and longevity. Key publications: 'The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance' (2015, Cell Metabolism) and 'MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline' (2021, Nature Communications). Pinchas Cohen is referenced as a foundational scientist in MOTS-c research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
🎓 Scientific Journal Author
Dr. Changhan David Lee, PhD
Changhan David Lee, PhD, is a Professor at the USC Leonard Davis School of Gerontology. He was the lead author on the seminal 2015 paper describing the discovery of MOTS-c (Cell Metabolism). His work established MOTS-c as an 'exercise mimetic' and identified its ability to translocate to the nucleus to regulate gene expression in response to metabolic stress. He has also investigated the immunomodulatory functions of MOTS-c, describing it as a host defense peptide. Key publications: 'MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance' (2015) and 'MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress' (2018, Cell Metabolism). Changhan David Lee is referenced as one of the leading scientists in MOTS-c research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
🔬 Contributing Researcher
Dr. Kelvin Yen, PhD
Kelvin Yen, PhD, is a researcher at the USC Leonard Davis School of Gerontology. He collaborates extensively with the Cohen lab to characterize mitochondrial-derived peptides (MDPs) including MOTS-c, investigating their roles in aging, healthspan, and metabolic regulation. Key publications: 'Mitochondrial Microproteins from Discovery to Function' (2025), 'Mitochondrially derived peptides as novel regulators of metabolism' (2017), and 'MOTS-c: an equal opportunity insulin sensitizer' (2019). Kelvin Yen is referenced as a contributing scientist in MOTS-c research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
Referenced Citations
Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015;21(3):443-454.
DOIReynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12(1):470.
DOIKim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metabolism. 2018;28(3):516-524.e7.
DOICohBar, Inc. CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity. BioSpace. 2021.
SourceKnoop A, Thomas A, Thevis M. Development of a mass spectrometry based detection method for the mitochondrion-derived peptide MOTS-c in plasma samples for doping control purposes. Rapid Communications in Mass Spectrometry. 2019;33(4):371-380.
DOIWan W, Zhang L, Lin Y, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. Journal of Translational Medicine. 2023;21(1):36.
DOIZempo H, Kim SJ, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1692-1717.
SourceKong BS, Min SH, Lee C, Cho YM. The mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes. Cell Reports. 2021;36(4):109447.
DOILu H, Tang S, Xue C, et al. Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation. International Journal of Molecular Sciences. 2019;20(10):2456.
DOIZhai D, Ye Z, Jiang Y, et al. MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA. Molecular Immunology. 2017;92:151-159.
PubMedYi X, Hu G, Yang Y, et al. Role of MOTS-c in the regulation of bone metabolism. Frontiers in Physiology. 2023;14:1149120.
DOIWei M, Gan L, Liu Z, et al. Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway. Cardiorenal Medicine. 2020;10(1):42-50.
PubMedPham TK, et al. MOTS-c restores mitochondrial respiration and cardiac function in type 2 diabetic cardiomyopathy. 2025.
PubMedYin Y, et al. MOTS-c attenuates inflammatory and bone cancer pain via AMPK-MAPK-c-fos signaling in spinal cord. 2020/2024.
PubMedKong BS, Lee H, L'Yi S, et al. Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes. Experimental & Molecular Medicine. 2025;57(8):1861-1877.
DOIYoon SH, Yuan F, Zhu X, et al. Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss. Journal of Clinical and Translational Endocrinology. 2026;43:100429.
DOIKim SJ, Miller B, Mehta HH, et al. The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiological Reports. 2019;7(13):e14171.
DOIKumagai H, Coelho AR, Wan J, et al. MOTS-c reduces myostatin and muscle atrophy signaling. American Journal of Physiology-Endocrinology and Metabolism. 2021;320(4):E680-E690.
SourceGao Y, Wei X, Wei P, et al. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023;13(1):125.
DOILee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radical Biology & Medicine. 2016;100:182-187.
DOIZheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Frontiers in Endocrinology. 2023;14:1120533.
DOIMohtashami Z, Singh MK, Salimiaghdam N, et al. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. International Journal of Molecular Sciences. 2022;23(19):11991.
DOIUSADA. What is the MOTS-c peptide? USADA.org. 2024.
SourceDieli-Conwright CM, et al. Effects of a 12 Week Breast Cancer Exercise Program on the Mitochondrial Derived Peptide MOTS-c. Scientific Reports. 2021.
PubMedStorage & Handling
Summary
Lyophilized powder: -18°C to -80°C, desiccated. Reconstituted: 4°C for 2–7 days; aliquot and freeze at -20°C for longer storage. Significant plasma instability (~25% loss at 4°C/24h, 85–90% at RT in 2–3h).
Recommended Laboratory Storage Conditions
Lyophilized Powder: Store in dry, cool, dark container at -18°C to -80°C, desiccated. Stable at room temperature for short periods (days) during shipping.
Reconstitution: Sterile water, bacteriostatic water, or dilute acetic acid. Do not shake vigorously to avoid degradation.
Solution: Refrigerate at 4°C; stable 2–7 days. For longer storage, aliquot and freeze at -20°C. Avoid repeated freeze-thaw cycles.
Stability: Plasma levels decrease ~25% at 4°C/24h and 85–90% at room temperature within 2–3 hours.
Forms: Lyophilized white powder in sealed vials (typically 10 mg); research-grade.
Handling: Allow vials to warm to room temperature before opening to prevent moisture condensation.
RUO Disclaimer
For Research Use Only (RUO). This product is intended solely for in-vitro research and laboratory experimentation. It is not a drug, food, cosmetic, or medical device and has not been approved by the FDA for any human or veterinary use. It must not be used for therapeutic, diagnostic, or any other non-research purpose. Pure US Peptide does not condone or encourage the use of this product for anything other than strictly defined research applications. Users assume full responsibility for compliance with all applicable regulations and guidelines.
Certificate of Analysis (COA)
Every batch is strictly tested by accredited third-party laboratories (ISO 17025) to ensure 99%+ purity.
Latest Lab Report
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