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Mitochondrial & longevity

MOTS-c

Also known as Mitochondrial Open Reading Frame of the 12S rRNA-c, MOTS-c (free base), MOTS-c acetate, MOTSc

Preclinical only

Mitochondrial-derived peptide (investigational; no approved product)

Not FDA-approved. Not on FDA's 503A category lists (May 14, 2026). Source, May 14, 2026

Identity. MOTS-c is a naturally occurring 16-amino-acid mitochondrial-derived peptide. FDA gives the sequence as H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH. FDA notes that the free base and the acetate salt are different bulk drug substances, and that the 2015-era nomination was inconsistent about which was meant. A vial labelled MOTS-c may be either. CB4211 (CohBar) is a different molecule. Its developer (CohBar, via BioSpace press release) describes it as 'a novel and improved analog of MOTS-c', and its structure has not been independently confirmed. Its data are not MOTS-c data. The formulary also carries MOTS-c in blends. Do not transfer the single-agent 5 mg / 25-unit regimen below to a blend. Dose blends from the MOTS-c mg per mL on the pharmacy label. The source does not say whether 5 mg is gross powder or net peptide, or which salt form it refers to.

At a glance

These dosages are a helpful guide, not a prescription. Every clinician is expected to do their own due diligence before prescribing.

No established human dose

No product containing MOTS-c is approved. FDA found no published human study of MOTS-c given by any route (May 2026 review). Evidence for exogenous dosing comes from mouse work (intraperitoneal). Human papers measure endogenous MOTS-c levels only. CB4211, an analog described by its developer, had a company-reported Phase 1a/1b (25 mg SC daily for 28 days in NAFLD). That study is not MOTS-c data. Clinic dosing rests on one provider blog. FDA found no in-vivo pharmacokinetic data, and an in-vitro study reports rapid hydrolysis in human blood. Whether exogenous dosing produces active concentrations is not established. The practice regimen is not derived from dose-response data, because FDA notes rodent studies did not assess dose-response in vivo.

No label or human study dosing exists for MOTS-c; FDA found no human dosing data for the exogenous peptide.
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What clinics and vendors publish

These ranges come from clinic and vendor publications, not studies.

Clinic-reported

This regimen comes from one source: a Florida aesthetic-medicine clinic blog (APRN author, updated Sept 17, 2026). It is not peer reviewed and gives no citations for its numbers. No trial or label supports it, and FDA found no human dosing data for exogenous MOTS-c. Other web pages checked state no MOTS-c dose at all. Treat this as one clinic's protocol, not a validated dose. The regimen is not derived from animal or human dose-response data. FDA notes rodent studies did not assess dose-response in vivo, and mouse doses cannot be scaled to this regimen. It applies to a single-agent MOTS-c vial only, not to blends.

StartClinic-reported
5 mg per injection, per one clinic protocol. That clinic's '25 units' applies only to a 10 mg vial reconstituted with 0.5 mL (20 mg/mL) on a U-100 1 mL syringe. Always dose in mg and mL (see reconstitution under handling).
TitrationClinic-reported
None. The dose is fixed at 25 units from the first injection, with no titration phase.
TypicalClinic-reported
5 mg per injection, 4 injections per cycle (20 mg per cycle), per one clinic protocol
CeilingClinic-reported
Not stated by the source; no ceiling dose identified in any source.
FrequencyClinic-reported
One injection every 5 days, 4 injections over 20 days (days 1, 6, 11, 16)
RouteClinic-reported
Subcutaneous, abdomen, rotating site
TimingClinic-reported
Morning, before the first meal
CycleClinic-reported
20 days on, then a 4-month break; about 2 cycles per year
  • Clinic-reportedPharmacy or clinic protocol1
    The dose is fixed at 25 units, equal to 5 mg , for the whole cycle. Frequency is one injection every 5 days , for 4 injections across a 20-day cycle, then a 4-month break. Injections go in the morning, before your first meal , subcutaneously in the abdomen with the site rotated each session.
  • Clinic-reportedPharmacy or clinic protocol1
    Starting point: dose is fixed at 25 units from the first injection. No titration phase. Draw 25 units on your 1 ml insulin syringe (5 mg per injection).
  • Clinic-reportedPharmacy or clinic protocol1
    On phase: 20 day protocol (4 injections, one every 5 days). Off phase: 4 months pause. Repeat: patients typically run 2 full cycles per year on this protocol.

Safety

Serious warnings

  • No label or boxed warning exists. FDA states potential safety risks of MOTS-c in humans are unknown, and it is particularly concerned about the lack of human data by any route.2
  • FDA is concerned about immunogenicity and peptide aggregation for a 16-amino-acid peptide given by subcutaneous injection. It found no clinical studies assessing either. Neutralizing antibodies could cause loss of efficacy or neutralize the endogenous counterpart.2
  • FDA states MOTS-c products are not well characterized physically or chemically. Peptide-related impurities and aggregates cannot be ruled out.2
  • No in-vivo pharmacokinetic data exist. FDA cites an in-vitro study reporting that MOTS-c is quickly hydrolyzed in human blood. This raises the question of whether exogenous administration produces pharmacologically active concentrations. Exposure from a 5 mg SC dose cannot be assumed.2
  • Dilution-dependent unit error: the 25-unit figure equals 5 mg only at 20 mg/mL. The same 10 mg vial in 1 mL (10 mg/mL) needs 50 units for 5 mg. In 2 mL (5 mg/mL) it needs 100 units. Drawing 25 units from a more dilute vial gives a 2x to 4x underdose.1

Contraindications

  • Clinic-protocol exclusions (not label contraindications): active cancer, pregnancy, bleeding disorders, uncontrolled diabetes.1
  • FDA identified no nonclinical reproductive/developmental or carcinogenicity studies, and no genotoxicity or repeat-dose toxicity studies. There are no data for lactation, renal impairment or hepatic impairment.2

Adverse effects

  • FDA searched FAERS through March 9, 2025 and returned no reports for MOTS-c. Absence of reports is not evidence of safety, because 503A compounders generally do not report.2
  • Analog data only, not MOTS-c (company-reported, SEC investor deck): CB4211 25 mg SC daily: injection site reactions 79% vs 33% with placebo, no serious adverse events. Persistent local drug deposition at the injection site led to interruption of the study to modify the formulation. The analog's dose and schedule are not comparable to the practice regimen.3

Monitoring

  • This is a prescriber-judgment inference from mouse insulin-sensitizing data. It is not trial-derived and not a validated protocol. Check glucose and HbA1c at baseline and on treatment in diabetic or prediabetic patients. Review concurrent glucose-lowering drugs for theoretical additive hypoglycemia (no human data). Inspect injection sites at each dose. Document baseline weight and metabolic markers. The clinic source says response markers and side effects are measured each cycle but does not name them.4

Handling

Reconstitution

One clinic protocol: a 10 mg vial plus 0.5 mL bacteriostatic water gives 20 mg/mL. A 5 mg dose is then 0.25 mL, or 25 units on a U-100 syringe. Dilution table for a 10 mg vial (arithmetic): 0.5 mL gives 20 mg/mL, and 5 mg = 0.25 mL = 25 units. 1 mL gives 10 mg/mL, and 5 mg = 0.5 mL = 50 units. 2 mL gives 5 mg/mL, and 5 mg = 1 mL = 100 units. Units apply only to the stated dilution. FDA reports MOTS-c acetate dissolves in water at 6.25 mg/mL, and the nomination gave no compounding instructions. A 20 mg/mL solution is therefore not established. At 6.25 mg/mL, a 5 mg dose is about 0.8 mL. Confirm the salt form and diluent volume with the dispensing pharmacy, and inspect for particulates. These figures are not from a pharmacy label. The pharmacy's instructions govern.

Storage before mixing

The FDA briefing reports that lyophilized MOTS-c (free base) is stable when stored at -20 C, desiccated and protected from light, in a tightly closed container. This comes from the literature, not a product label.

Storage after mixing

The FDA briefing reports a recommendation of +4 C for 2-7 days after reconstitution, and below -18 C for future use. A clinic page says to store the reconstituted vial refrigerated and use it within the 20-day protocol window. The two do not agree. As a practical option, reconstituting the second vial around day 11 rather than day 1 keeps any vial under about 6 days, consistent with the reported 2-7 day range. This is an inference, not a sourced instruction. The pharmacy label governs.12

Evidence

No product containing MOTS-c is approved. FDA found no published human study of MOTS-c given by any route (May 2026 review). Evidence for exogenous dosing comes from mouse work (intraperitoneal). Human papers measure endogenous MOTS-c levels only. CB4211, an analog described by its developer, had a company-reported Phase 1a/1b (25 mg SC daily for 28 days in NAFLD). That study is not MOTS-c data. Clinic dosing rests on one provider blog. FDA found no in-vivo pharmacokinetic data, and an in-vitro study reports rapid hydrolysis in human blood. Whether exogenous dosing produces active concentrations is not established. The practice regimen is not derived from dose-response data, because FDA notes rodent studies did not assess dose-response in vivo.

Mechanism

MOTS-c is reported in mice to act mainly on skeletal muscle. It inhibits the folate cycle and de novo purine biosynthesis, which activates AMPK and improves insulin sensitivity and metabolic homeostasis. This mechanism comes from preclinical work. FDA states the molecular target is unknown.24

Availability

Amounts offered

  • 10 mg

Custom strengths on request.

References

According to PubMed

  1. 1MOTS-c Dose: Vial Concentration, BAC Water, and Syringe Units (Perfect B Aesthetic Medicine, V. Marulanda APRN, updated Sept 17, 2026)Perfect B Aesthetic Medicine clinic blog, 2026
  2. 2FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate)U.S. Food and Drug Administration (evaluation dated May 11, 2026), 2026
  3. 3CohBar, Inc. Q2 Investor Presentation, August 10, 2021 (Exhibit 99.3): CB4211 Phase 1a/1b toplineSEC EDGAR filing, 2021
  4. 4The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.Cell Metabolism 21(3):443-454, 2015
  5. 5Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (Categories 1-3), Updated May 14, 2026U.S. Food and Drug Administration, 2026
  6. 6Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act (page content current as of 05/14/2026)U.S. Food and Drug Administration, 2026
  7. 7MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.Nature Communications 12(1):470, 2021
  8. 8The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity.Physiological Reports 7(13):e14171, 2019
  9. 9Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.Scientific Reports 11(1):16916, 2021
  10. 10A Phase 1a/1b Study of Safety, Tolerability, and Pharmacokinetics of CB4211 (NCT03998514)ClinicalTrials.gov registry, CohBar, Inc., 2021
  11. 11PEPTIDE-L WAVE! PCAC Approves Four Bulk Drug Substances for the 503A List (reports MOTS-c 7-5-2 vote, July 23, 2026)The FDA Law Blog (secondary source), 2026

Last reviewed 2026-10-14. 28 figures checked against their sources. How this works