MOTS-c

Overview

MOTS-c is an investigational mitochondrial-derived peptide studied preclinically for metabolic regulation. It is research-only and not FDA-approved; the CB4211 analog program (CohBar) was discontinued in 2023.

Mechanism of Action

MOTS-c activates AMPK primarily in skeletal muscle, partly via inhibition of the folate cycle and de novo purine biosynthesis (AICAR accumulation), increasing glucose uptake and fatty acid oxidation. Interaction with the folliculin–FNIP complex has been proposed. Serum MOTS-c declines with age, obesity, and type 2 diabetes, supporting a proposed endocrine role.

Research Summary

Lee et al. (Cell Metabolism, 2015; PMID 25738459) identified MOTS-c and showed that exogenous administration in mice prevented diet-induced obesity and insulin resistance via AMPK activation in skeletal muscle. Kim et al. (Cell Metabolism, 2018; PMID 29983246) demonstrated that MOTS-c translocates to the nucleus under metabolic stress and regulates antioxidant response element (ARE) genes. Reynolds et al. (Nature Communications, 2021; PMID 33473109) reported that exercise induces MOTS-c in human skeletal muscle and that MOTS-c treatment improved physical capacity in young, middle-aged, and aged mice. Human clinical data are limited to CohBar's Phase 1a/1b study of the analog CB4211 in healthy volunteers and obese NAFLD subjects, which reported acceptable tolerability and exploratory signals on ALT/AST and glucose; CohBar wound down the program in 2023. No completed Phase 2 or Phase 3 trials exist for MOTS-c or its analogs, and grey-market dosing (typically ~10 mg SubQ 2-3x/week) is not clinically validated.

Vendors selling MOTS-c

Scored vendors carrying MOTS-c, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Prescribers who offer MOTS-c

101 prescribers in our directory work with MOTS-c, each confirmed from their own website. Peptides like MOTS-c require a prescription from a licensed provider — telehealth options are available.

Reported Side Effects

• Limited human safety data for native MOTS-c
• Injection-site reactions (anecdotal)
• Theoretical concerns from AMPK activation and altered mitochondrial signaling
• No serious adverse events reported in the Phase 1a/1b study of the analog CB4211, but that program was discontinued and native MOTS-c has not been systematically evaluated in humans

Biomarkers researchers track for MOTS-c

These biomarkers appear in the research literature as measures of response and safety for this compound.

Related Peptides

Research Guides

• Cheapest verified MOTS-c: live prices, vendors & COA data

Compare MOTS-c with Others

Research References

• Lee C, et al. Cell Metabolism. 2015;21(3):443-454. (PMID 25738459)
• Kim KH, et al. Cell Metabolism. 2018;28(3):516-524. (PMID 29983246)
• Reynolds JC, et al. Nature Communications. 2021;12(1):470. (PMID 33473109)

Frequently asked questions

Has MOTS-c been independently lab-tested?

Disclosed Labs has collected 202 Certificates of Analysis (COA) for MOTS-c from 16 independent testing labs. 48 vendors have submitted material for testing. Products average 99.5% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/mots-c/testing.

What is the average purity of MOTS-c on the market?

Based on 202 COAs analyzed by Disclosed Labs, MOTS-c products average 99.5% (±0.3%) tested purity. Individual vendor results vary; see per-vendor COA data at https://www.disclosedlabs.com/peptides/mots-c/coas.

Which labs have tested MOTS-c?

Independent labs that have tested MOTS-c include: ILS Labs (Grade A), Ethos Analytics (Grade B). Full lab credibility grades and profiles are at https://www.disclosedlabs.com/labs.

Where can researchers source MOTS-c?

8 vendors with Disclosed Labs trust grades currently list MOTS-c, including Glacier Aminos, Voltera Sciences, Ion Peptide. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/mots-c.

Which prescribers offer MOTS-c with a prescription?

101 prescribers in the Disclosed Labs directory work with MOTS-c, each confirmed from their own website, with telehealth options available. MOTS-c requires a prescription from a licensed provider. Browse them at https://www.disclosedlabs.com/prescribers?peptide=MOTS-c.

How does MOTS-c work?

MOTS-c activates AMPK primarily in skeletal muscle, partly via inhibition of the folate cycle and de novo purine biosynthesis (AICAR accumulation), increasing glucose uptake and fatty acid oxidation. Interaction with the folliculin–FNIP complex has been proposed. Serum MOTS-c declines with age, obesity, and type 2 diabetes, supporting a proposed endocrine role.

What does the research say about MOTS-c?

Lee et al. (Cell Metabolism, 2015; PMID 25738459) identified MOTS-c and showed that exogenous administration in mice prevented diet-induced obesity and insulin resistance via AMPK activation in skeletal muscle. Kim et al. (Cell Metabolism, 2018; PMID 29983246) demonstrated that MOTS-c translocates to the nucleus under metabolic stress and regulates antioxidant response element (ARE) genes. Reynolds et al. (Nature Communications, 2021; PMID 33473109) reported that exercise induces MOTS-c in human skeletal muscle and that MOTS-c treatment improved physical capacity in young, middle-aged, and aged mice. Human clinical data are limited to CohBar's Phase 1a/1b study of the analog CB4211 in healthy volunteers and obese NAFLD subjects, which reported acceptable tolerability and exploratory signals on ALT/AST and glucose; CohBar wound down the program in 2023. No completed Phase 2 or Phase 3 trials exist for MOTS-c or its analogs, and grey-market dosing (typically ~10 mg SubQ 2-3x/week) is not clinically validated.