MOTS-c

What it is

MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial 12S ribosomal RNA gene [1]. Lee and colleagues reported it in 2015, showing that mitochondrial DNA can encode a signalling peptide that acts on the rest of the body rather than only inside the organelle [1]. The peptide is present in plasma and in many tissues, and circulating amounts fall with age [3]. In people it behaves like an exercise signal: amounts in skeletal muscle and in blood climb during and after hard exertion [2]. No MOTS-c product has ever been approved by FDA, and compounded preparations are not FDA-approved drugs [11].

How it works

In cell and mouse experiments MOTS-c interferes with folate-dependent one-carbon metabolism and the purine synthesis pathway attached to it, which activates AMP-activated protein kinase, the cell’s low-energy sensor [1]. Skeletal muscle appears to be its main target organ [1]. Under metabolic stress the peptide moves into the nucleus and shifts expression of stress-response genes, including heat-shock genes [2]. Reviews summarise further preclinical effects on glucose handling, fat use, inflammation and ageing tissue [3]. Separate bone work reports that MOTS-c pushes osteoblasts toward proliferation and mineralisation while restraining osteoclast formation [4]. All of this is laboratory and animal mechanism, and reviewers note that no effective clinical method of use has been developed [3].

What the evidence shows

Human data are observational rather than interventional [3]. In ten sedentary healthy young men who completed a bout of cycling exercise, MOTS-c in skeletal muscle rose 11.9-fold after exercise, while circulating amounts rose about 1.6-fold during and 1.5-fold after the bout before returning to baseline after four hours of rest [2]. Treatment data come from animals: in mice, MOTS-c prevented diet-induced obesity and age-dependent insulin resistance [1]. The nearest human treatment study used CB4211, a modified analogue of MOTS-c rather than the peptide itself, in a phase 1 study of 88 participants including people with non-alcoholic fatty liver disease, completed in April 2021 [5]. FDA reviewers proposed against listing MOTS-c [7].

Regulatory status

Not an FDA-approved drug. On Jul 23–24 2026 the FDA Pharmacy Compounding Advisory Committee voted to recommend adding it to the 503A bulk drug substances list; FDA has not finalized that listing (as of Sep 24 2026). [6] The MOTS-c vote was 7 in favour, 5 against and 2 abstentions, for a proposed use in obesity and osteoporosis [8][9]. FDA scientists had proposed the opposite [7]. In April 2026 FDA removed MOTS-c from Category 2 of its 503A nominations list after the nomination was withdrawn, which did not place it on the bulks list [10]. Formal listing needs notice-and-comment rulemaking that could run into 2027 or later, and listing is not FDA approval [9].

Half-life and what it means for a level curve

We found no published human pharmacokinetic study of MOTS-c; the review literature covers preclinical work and notes that no effective clinical method of use has been developed [3]. STACK has no reference half-life for this compound because no human value has been published; you can enter your own estimate. The phase 1 study of the analogue CB4211 listed apparent terminal elimination half-life among its measures, but results are not posted on ClinicalTrials.gov and CB4211 is a different molecule [5]. If you enter an estimate, the chart rises at each logged dose and decays between doses, approaching about 97% of steady state after roughly five half-lives on a regular schedule. STACK’s curve is an estimate from this published half-life, not a blood level.

Reported side effects

There is no approved label for MOTS-c and no controlled human safety study of the peptide itself, so a conventional adverse-reaction list does not exist [3]. FDA’s briefing document for the July 2026 meeting proposed that MOTS-c not be added to the 503A list [7]. At that meeting FDA scientists argued against all of the nominated peptides, citing insufficient safety and efficacy information and incomplete characterisation of the molecules [9]. When FDA placed this group of peptides in Category 2 in September 2023 it cited immunogenicity, impurities and limited human clinical data [9]. Compounded drugs are not FDA-approved, and FDA does not verify their safety, effectiveness or quality before they are marketed [11]. Tell your prescriber about anything unexpected.

Storage and handling

MOTS-c has no FDA-approved label, so the compounding pharmacy’s label is the authority on storage, beyond-use date and handling [11]. Drugs compounded under section 503A are exempt from current good manufacturing practice requirements, and day-to-day oversight of state-licensed pharmacies sits with state boards of pharmacy, which is why the printed label and the pharmacist’s written instructions carry the weight an approved package insert would carry elsewhere [11]. FDA notes that poor compounding practice can lead to contamination or to a preparation containing too much or too little active ingredient [11]. Follow the storage temperature and the beyond-use date on your own label, and ask the pharmacy if either is missing. STACK’s reconstitution calculator does the mixing arithmetic.

What STACK tracks for it

STACK logs each dose exactly as your prescriber wrote it, with the date, time and injection site, so you can see rotation at a glance. Because no human half-life has been published, the estimated-level chart stays off until you enter your own half-life estimate [3]. You can record the schedule your prescriber gave you and mark doses against it, track weight and any side effects you notice, and keep vial inventory with reconstitution details so the app knows what is in each vial. Notes and side-effect entries export as a plain summary you can take to your next appointment. STACK shows what you logged; it does not prescribe, and it does not suggest amounts.

The reference half-life in STACK

STACK ships MOTS-c without a default half-life: No published human value; human pharmacokinetics never measured. You enter your own estimate before a curve is drawn.

Estimate only. Modelled from the published half-life you selected and the doses you logged — not a measured blood level. Do not use it to make medication decisions.

Free tools for MOTS-c

Read next

Sources

Every URL below was fetched and checked on 2026-09-24. Bracketed numbers in the text link here.

1. OtherThe mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
2. OtherMOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
3. ReviewMOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
4. ReviewRole of MOTS-c in the regulation of bone metabolism
5. TrialA Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (NCT03998514)
6. FDAJuly 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee
7. FDAFDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24 2026
8. OtherFDA advisory committee backs two more peptides, rejects one for compounding list
9. OtherBulk List Bound: PCAC Backs Majority of Peptides in Two-Day Public Meeting
10. OtherFDA Announces Removal of 12 Peptides from Category 2 and Schedules PCAC Meetings
11. FDACompounding and the FDA: Questions and Answers