What is MOTS-c?

What sources report

Origin and structure

MOTS-c is short for mitochondrial open-reading-frame of the twelve S rRNA type-c.¹⁵ A 51-base-pair stretch of the mitochondrial 12S rRNA gene codes for it, and the peptide is 16 amino acids long (MRWQEMGYIFYPRKLR).⁶⁷ Lee and colleagues reported it in 2015 as a regulator of insulin sensitivity and metabolic balance.⁵ Its formula is C101H152N28O22S2, with a molar mass of 2174.6 g/mol.⁸

It belongs to the mitochondrial-derived peptides.¹ A related peptide, humanin, was found in 2001 and comes from the 16S rRNA gene instead.⁶ The body makes MOTS-c itself, and it can be measured in human and rodent blood.⁵ Research products are synthetic copies.¹ FDA treats the free base and the acetate salt as two different ingredients, so the salt form on a label matters.¹

How it is thought to work

The mechanism work so far comes from cells grown in the lab and from mice.⁵⁹¹⁰ In the 2015 work, skeletal muscle appeared to be the main target in mice.⁵ In a human kidney cell line, MOTS-c slowed the folate cycle and the purine production linked to it, which switched on AMPK, an enzyme that senses cell energy.⁵¹ That slowdown can make AICAR, a known AMPK activator, build up inside cells.¹

Later studies added detail. Under glucose restriction, MOTS-c moved into the cell nucleus and helped regulate many genes, including antioxidant-response genes, in a 2018 cell study.⁹ A 2024 study reported that it binds and activates an enzyme called CK2 in cell-free tests.¹⁰ In mice, its protection against muscle wasting weakened when CK2 was suppressed.¹⁰

Big gaps remain. FDA reviewers wrote in May 2026 that its molecular targets are unknown, so it is hard to predict which organs it affects; their review does not cite the 2024 CK2 study.¹ FDA found no pharmacokinetic studies in animals or people.¹ In human blood in a test tube, MOTS-c broke down quickly into shorter pieces, and whether injected MOTS-c can reach active levels in people over time has not been determined.¹

How strong the evidence is

Human evidence is thin: FDA found no clinical studies or human exposure data by any route.¹ Blood levels are also hard to compare, because a mass spectrometry test could not confirm levels measured with ELISA.¹³ A 2023 review noted that no effective way of using MOTS-c in the clinic has been developed.¹⁴ In short, the treatment studies show effects in rodents, not in people.¹ Full list with evidence levels: MOTS-c benefits and uses.

A related analog, CB4211

CB4211 is a modified analog of MOTS-c developed by the company CohBar.¹⁵ Unlike MOTS-c, it has been through a human trial, a phase 1a/1b study with 88 participants.¹⁶ No results are posted on ClinicalTrials.gov.¹⁶

Side effects

No completed clinical trial has reported MOTS-c side effects, and FDA found no human safety data and no toxicity studies.²¹ USADA's summary of side effects reported by people who claim to have bought it online includes a fast heart rate or palpitations, injection site irritation, insomnia, immune reactions and fever.² One concern FDA names is that injected MOTS-c could trigger an immune response because of aggregates or impurities.¹ Full list: MOTS-c side effects.

Dosage information

No human dose of MOTS-c has been established.¹ Published doses come from rodent studies that injected 0.5 to 15 mg/kg into the abdominal cavity (intraperitoneal).⁵¹²¹ FDA found that those studies did not assess how effects change with dose.¹ A phase 2a trial registered in 2026 gives a fixed daily dose under the skin for 12 weeks, but the registry does not state the amount.⁴ Full details: MOTS-c dosage.

Reconstitution and storage

The MOTS-c for sale on this site is a 10 mg vial of freeze-dried powder; diluent is sold separately. FDA's 2026 review, citing supplier data, says the dry free base is stable at -20°C when desiccated, protected from light and tightly closed.¹ Once reconstituted, the solution is recommended to be kept at +4°C for 2 to 7 days, or below -18°C for later use.¹

Two cautions come from the same review. Water solubility is reported (6.25 mg/mL for the acetate salt), yet no data show that MOTS-c dissolves completely in a finished solution.¹ Peptides can also clump or degrade when pH, temperature, concentration, impurities or other ingredients change.¹

Concentration is plain division, and it is lab arithmetic, not a dose. For example, 10 mg in 2 mL of diluent gives 5 mg/mL. The reconstitution guide covers the lab steps, the reconstitution calculator does the math, and how to store peptides covers cold storage.

Regulatory status

MOTS-c is not an FDA-approved drug.¹ No USP or National Formulary monograph exists for it or its acetate salt, and neither is part of an approved drug.¹ USADA adds that it is not approved for use in humans or in compounded medications.²

Its compounding status moved several times in 2026:

• April 15. HHS Secretary Kennedy confirmed that MOTS-c was one of 12 peptides removed from FDA's category 2 after their nominations were withdrawn.¹⁷ Leaving category 2 does not automatically grant category 1 status.¹⁷
• April. FDA's page on bulk substances that may present significant safety risks, current as of April 22, lists MOTS-c among substances whose nominations were withdrawn, with possible immunogenicity, peptide-related impurities and characterization problems.¹⁸
• May 11. FDA reviewers proposed not adding MOTS-c free base or acetate to the 503A bulks list, which names the substances compounding pharmacies may use. They cited poor characterization, no human safety or effectiveness data and no toxicity studies.¹
• July 23. The Pharmacy Compounding Advisory Committee reviewed MOTS-c for obesity and osteoporosis and voted 7 to 5, with 2 abstentions, to recommend adding it.¹⁹²⁰ FDA staff scientists had opposed adding any of the peptides reviewed.³
• Since the vote. The recommendation is not binding, and FDA must publish proposed rules for public comment first.³ As of October 14, a law firm reported, FDA had not announced whether it will begin that rulemaking.²¹ The same firm cited reports that the administration is exploring an interim enforcement discretion policy that would let compounding pharmacies prepare certain peptides, and said it is uncertain whether FDA will issue one.²¹

Other points from the record:

• Outsourcing facilities reported no compounded products containing MOTS-c from January 2017 to December 2025.¹
• FDA's search found no products containing MOTS-c authorized by the European Medicines Agency.¹
• In sport it is prohibited at all times under section 4.4.1 (activators of AMPK) of the World Anti-Doping Agency Prohibited List, and USADA says a therapeutic use exemption is highly unlikely.²
• In a December 2024 warning letter to an online peptide seller, FDA wrote that despite research-use-only labeling, evidence from the seller's websites showed the products were intended as drugs for human use.²² The letter named other peptides, not MOTS-c. For what that label covers, see What are research peptides?