Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of FOXO4-DRI and MOTS-c — mechanism, side effects, legal status, and pricing.
FOXO4-DRI is a D-retro-inverso peptide designed to disrupt the FOXO4-p53 interaction in senescent cells. It is studied as a senolytic agent that selectively induces apoptosis in senescent cells while sparing normal cells.
MOTS-c is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 12S rRNA, discovered by Lee and Cohen at USC in 2015 (sequence: MRWQEMGYIFYPRKLR). It is an investigational, research-only peptide studied as a metabolic regulator; it has not been approved by the FDA for any indication.
FOXO4-DRI
MOTS-c
Category
Legal Status
Mechanism
Half-life
Side Effects
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
FOXO4-DRI
MOTS-c
COA corpus from Disclosed Labs — independently tested batches only.
FOXO4-DRI
5
COAs
99.5%
Avg purity
4
Labs
MOTS-c
193
COAs
99.5%
Avg purity
16
Labs
Baar et al. (Cell, 2017, PMID 28340339) identified FOXO4 as a pivot for senescent-cell viability and designed a cell-penetrating D-retro-inverso peptide that disrupts the FOXO4-p53 interaction, selectively triggering apoptosis in senescent cells while sparing proliferating cells. In vivo, the peptide neutralized doxorubicin chemotoxicity and, in fast-aging XpdTTD/TTD and naturally aged mice, restored fur density, renal function, and fitness. This is the only primary in vivo study; evidence is preclinical only. No human clinical trials have been registered or completed. Safety in humans is unknown — as a systemic senolytic inducing apoptosis, theoretical risks include impaired wound healing, immune perturbation, and off-target effects on quiescent stem-cell populations.
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.
FOXO4-DRI and MOTS-c are both in the Metabolic category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Contraindications
Lab Testing
Disclosed Labs