MOTS-c

Areas of active research — not promised effects

Each tag links to other compounds with research into that goal. Research use only: these are areas of study, not human-use claims.

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MOTS-c is not FDA-approved for any human therapeutic use and holds no active IND. It was among the 19 peptides designated to the FDA 503A Category 2 (do-not-compound) list. Effective April 15, 2026, FDA removed MOTS-c (free base and acetate salt forms) from Category 2, removing it from the explicit prohibition on compounding. However, removal from Category 2 does not authorize compounding — the Pharmacy Compounding Advisory Committee (PCAC) is scheduled to review MOTS-c at its July 23–24, 2026 meeting to determine whether it should be added to the 503A Bulk Drug Substances list permitting compounding. Until that determination is issued and finalized, compounding of MOTS-c remains in a regulatory grey zone. Sale or supply for human therapeutic use outside an approved IND is not authorized.

Transparent blend · bci-1.0 · never paid-placement

Primary name

MOTS-c

Origin

MOTS-c (Mitochondrial ORF of the 12S rRNA-c) is encoded within the 12S ribosomal RNA (MT-RNR1) region of the human mitochondrial genome. It was first characterized in 2015 by Lee et al. and is one of the best-studied members of the mitochondrial-derived peptide (MDP) family alongside humanin and the SHLP series. The peptide is expressed endogenously in multiple tissues and circulating levels increase in response to exercise and metabolic stress.

Registry IDs

PubChem CID

146675088

CAS

1627580-64-6

InChIKey

WYTHCOXVWRKRAH-LOKRTKBUSA-N

Molecular formula

C101H152N28O22S2

Molar mass

2174.6 g/mol

Monoisotopic

2173.1077409 Da

InChIKey

WYTHCOXVWRKRAH-LOKRTKBUSA-N

Appearance

White to off-white lyophilized powder

Solubility

Water-soluble; readily dissolves in sterile water, PBS, or physiological saline.…

Sequence not available in current seed.

Stability: As a 16-mer peptide with no disulfide bonds, MOTS-c is susceptible to proteolytic degradation in biological matrices and plasma. The lyophilized form is stable

Vial sizes

5 mg

Purity grades

>95% / >98%

Salt forms

Free base (primary)

• GHS hazard class on file
• PPE & spill response
• Disposal guidance
• Not-for-human-consumption posture

How much research exists, and of what maturity — never a verdict on whether it works.

Mechanism of action

• MOTS-c primarily operates through the folate-AICAR-AMPK signaling axis: the peptide inhibits the folate cycle, leading to accumulation of the purine synthesis intermediate AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), which in turn activates AMP-activated protein kinase (AMPK)
• AMPK activation triggers downstream effects including enhanced glucose uptake, increased fatty acid oxidation, suppression of gluconeogenesis, and promotion of mitochondrial biogenesis
• Under cellular stress, MOTS-c also translocates from the cytoplasm to the nucleus, where it binds and upregulates antioxidant response element (ARE)-driven stress-adaptation genes, functioning as a retrograde mitochondrial stress signal
• In preclinical models of type 2 diabetes, exogenous MOTS-c administration has been shown to restore mitochondrial respiration and improve insulin signaling in skeletal muscle, liver, and adipose tissue

Pharmacokinetics (ADME)

Half-life

Not formally established in humans. Animal study data suggest rapid systemic clearance consistent with other small peptides; precise half-life values have not been published.

Clearance

No published pharmacokinetic clearance data in humans or primates. Rapid proteolytic degradation is expected in biological matrices.

PK–PD note: No formal human PK study has been published as of May 2026. Preclinical dosing studies in rodents have used once-daily or every-other-day subcutaneous injections over multi-week periods, suggesting a …

Reading the evidence

• Evidence quality and gaps vary by application — see the cited grades above.
• Indexed-article counts span all evidence tiers, not only completed human trials.
• No first-party human-dosing, efficacy, or benefit claims are made here.

Key reviews & evidence-gap sources

• Zhou Q, et al. The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis. Diabetology & Metabolic Syndrome. 2024;16:200. — Systematic review/meta-analysis; PROSPERO CRD42021248167; 7 studies, 602 participants; circulating MOTS-c reduced in diabetes, increased in obesity.
• Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol. 2023;14:1120533. — Narrative review covering discovery, physiological function, mechanisms (AMPK, nuclear translocation), and therapeutic applications.
• Alzheimer's Drug Discovery Foundation Cognitive Vitality Report: MOTS-c — Independent assessment; states no clinical trials testing MOTS-c or analogs at time of report (pre-NCT07505745; predates Phase 2a).
• Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes & Metabolism Journal. — Notes MOTS-c as first mitochondrial-encoded peptide subjected to clinical trials; references CB4211 (NCT03998514) for fatty liver/obesity.

4 registered trials — 2 currently recruiting.

—
NCT03878706
The Cardiovascular Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination

RECRUITING

Phase 2
NCT07505745
MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

RECRUITING

—
NCT04027712
Platelet Reactivity, B-amyloid, MOTS-c and Mortality of Type II Diabetics With CAD

UNKNOWN

—
NCT06133946
Cohort Of DEafness-gene Screening

ACTIVE_NOT_RECRUITING

Summary (literature)

No formal human safety or toxicology trials for MOTS-c have been published as of May 2026. In rodent studies, MOTS-c was well tolerated across the dose ranges reported in efficacy studies (0.5–15 mg/kg in mice). As an endogenous peptide, acute immune reactivity is considered low.…

WADA status

Prohibited. WADA classifies MOTS-c as prohibited at all times under Section S4 (Hormone and Metabolic Modulators), specifically under AMPK activators, effective…

Dominant research route: Intraperitoneal (IP) injection in mouse preclinical models; subcutaneous (SC) is the route used in the (analog) human trial and the recruiting native-MOTS-c Phase 2a.

Acute and chronic IP injection in mice (e.g., 7-day IP injections for glucose tolerance; 2.5 mg/kg IP twice daily for 3 days; formalin test antinociception)

Bioavailability: IP was the standard systemic delivery route in foundational preclinical mouse studies; no human IP data. Bioavailability not characterized as a PK endpoint in these studies.

Dominant preclinical route. Cell Metabolism 2015 (Lee et al.) treated mice with IP MOTS-c for 7 days then glucose tolerance test; Kim 2019 (Physiological Reports) used 2.5 mg/kg IP twice daily for 3 days; Frontiers review notes IP injection reduced formalin-test licking time dose-dependently.

Human Phase 1a/1b of CB4211 (a MOTS-c analog) via SC injection, completed 2021 (NCT03998514, n=88); Phase 2a of native MOTS-c via SC, recruiting 2026 (NCT07505745, target n=120). Also mouse SC osmotic-pump studies.

Bioavailability: CB4211 Phase 1a/1b assessed safety, tolerability, and PK of single- and multiple-ascending SC doses (Parts A–C); Part C gave once-daily SC for 28 days in NAFLD. Native MOTS-c Phase 2a uses fixed once-daily SC for 12 weeks. No native-MOTS-c human PK has been published as completed.

CB4211 is an analog of MOTS-c, not native MOTS-c — the only completed human SC trial is for the analog. The native-MOTS-c Phase 2a (Hudson Biotech, NCT07505745) is recruiting, not completed. Mouse SC data exist (e.g., osmotic-pump delivery in TAC cardiac model).

No dedicated oral PK or oral-stability study of MOTS-c identified in primary literature; general peptide-oral-delivery barrier science applies.

Bioavailability: As a 16-amino-acid peptide, MOTS-c is expected to be susceptible to gastrointestinal enzymatic degradation and poor epithelial permeability; no oral bioavailability figure has been published for MOTS-c itself.

Oral-stability reasoning is inferred from general peptide pharmacology, not from a MOTS-c-specific oral study. Oral stability ≠ oral absorption; no MOTS-c oral absorption data exist.

Animal & human figures are kept visibly separate so studied animal doses are never misread as human guidance.

Sorted A–Z by vendor — never by price

Weekly median $/mg from the live vendor crawl.

Researched storefront prices, bucketed

p25 $4.18 · median $9.45 · p75 $10.75 · 7 researched vendors

Legit, COA-backed band: $8.50–$12.00/mg.

Value rule: don't just buy the cheapest — a price under $3/mg is a red flag. Pair price with COA and independent-test grade.

Estimated cost of research (10 mg)

Vial (best researched price)

$34

Bacteriostatic water (generic estimate)

$6

Syringes / supplies (generic estimate)

$12

What each test proves — general guidance, plus this compound's researched purity data

Purity on the current market (researched)

~99.0–99.96% HPLC purity across independent third-party lab tests (Janoshik and Kovera Labs) of vendor batches.

Independent labs cited for this compound

No FDA recalls or market withdrawals specific to MOTS-c were found in the retrieved sources.

Buyer red-flag checklist

• Not FDA-approved for any indication; unlawful for use in compounded medications under FDA's 503A framework (FDA proposed not adding to Bulks List July 2026).
• Listed on the WADA Prohibited List (Section 4.4 Metabolic Modulators / AMPK activators), prohibited in- and out-of-competition; no Therapeutic Use Exemption available.
• FDA flagged potential significant immunogenicity risk for injectable use due to aggregate formation and peptide-related impurities; no human safety data by any route.
• Widely sold online 'for research purposes only' as an injectable for weight loss/bodybuilding despite no completed human clinical trials.
• No documented history of human compounding use was established in FDA's review.
• Grey-market reports of fabricated/falsified Certificates of Analysis and underdosed product exist but are anecdotal and not independently quantified.

GMP vs research-grade: the chemistry (SPPS + HPLC + MS) is identical — the difference is the quality system.

Underdosing / mislabeling: No independent aggregate underdosing prevalence figure for MOTS-c was located from Janoshik/MZ Biolabs/Finnrick-style public test aggregates; individual published COAs (e.g., Panda Peptides MOTS-c at 99.043% HPLC, New Wave Peptides batch 19470/A at 99.866%, Peptide Partners via Kovera Labs at 99.964%) report purity but do not constitute a prevalence estimate.

• An RUO label is not an import exemption — CBP judges actual intended use.
• Lyophilized powder is ambient-stable in transit; temperature control needed for > 7-day transit.
• US-warehouse vendors dodge import scrutiny — they cost more but ship more reliably.

Every item dated & sourced

Prohibited at all times (in- and out-of-competition) under Section S4.4.1, Activators of the AMP-activated protein kinase (AMPK); MOTS-c named as an example ("mitochondrial open reading frame of the 12S rRNA-c") on the WADA Prohibited List. No Therapeutic Use Exemption (TUE) available because there is no approved therapeutic use.

No granted patents identified in current seed. Composition-of-matter coverage is limited given the peptide's synthetic origin.

• IACUC / IRB research context
• RUO buyer responsibilities & documentation
• Veterinary / alternative-use where lawful
• Jurisdiction-aware "who may lawfully obtain"

What people discuss

Reported concerns — discussion, not established effects

Reading caveats

• Affiliate / referral-code promotion on YouTube
• Exercise-in-a-vial marketing hype
• Anecdotal self-experimentation without controls
• No completed human RCTs cited in most user claims

Manually researched from reddit, youtube, x, bluesky— theme weights are research estimates, not live counts; aggregated & de-identified. No individual posts, quotes, or usernames are ever shown.

Relative research / market volume — populated once the activity stream is wired

Inline tooltips for lyophilized, RUO, EU/mg, SPPS, 503A and more.

Toggle plain-language ↔ scientific in the header.

• How to read a COA
• Free base vs acetate
• Understanding evidence grades

Mitochondria-encoded 16-mer peptide activating AMPK via the folate-AICAR axis; studied for metabolic regulation, insulin sensitivity, and exercise adaptation. Approximately 240 articles are indexed (literature last scanned 2026-05-29). US regulatory status: Research Use Only — not FDA-approved; removed from Category 2, pending PCAC review. Research use only.

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