Mots C: Safety Profile & 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.
References
- 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.
- Reynolds 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.
- Kim 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.
- CohBar, Inc. CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity. BioSpace. 2021.
- Knoop 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.
- Wan 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.
- Zempo 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.
- Kong 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.
- Lu 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.
- Zhai 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.
- Yi X, Hu G, Yang Y, et al. Role of MOTS-c in the regulation of bone metabolism. Frontiers in Physiology. 2023;14:1149120.
- Wei 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.
- Pham TK, et al. MOTS-c restores mitochondrial respiration and cardiac function in type 2 diabetic cardiomyopathy. 2025.
- Yin Y, et al. MOTS-c attenuates inflammatory and bone cancer pain via AMPK-MAPK-c-fos signaling in spinal cord. 2020/2024.
- Kong 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.
- Yoon 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.
- Kim 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.
- Kumagai 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.
- Gao Y, Wei X, Wei P, et al. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023;13(1):125.
- Lee 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.
- Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Frontiers in Endocrinology. 2023;14:1120533.
- Mohtashami 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.
- USADA. What is the MOTS-c peptide? USADA.org. 2024.
- Dieli-Conwright CM, et al. Effects of a 12 Week Breast Cancer Exercise Program on the Mitochondrial Derived Peptide MOTS-c. Scientific Reports. 2021.
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This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.
