MOTS-c vs SHLP-2
MOTS-c has human endogenous-peptide observations and a native Phase 2 registration without outcomes; SHLP-2 has receptor and metabolic model findings with no established human treatment effect.
Last updated: September 28, 2026
Dossier labels summarize each dossier's research scope. They do not establish comparative treatment benefit or safety. Read the comparison below in that context.
MOTS-c
Dossier overview
SHLP-2
Dossier overview
Research comparison
MOTS-c is a 16-residue mitochondrial peptide whose original study examined metabolism and AMPK-related signaling in cells and mice. SHLP-2 is a humanin-like peptide from the mitochondrial 16S region; its model research has investigated cytoprotection and energy regulation. These are different sequences, not interchangeable formulations. MOTS-c discovery, PMID 25738459 · SHLP-2 receptor study, PMID 37468558
| Question | MOTS-c | SHLP-2 |
|---|---|---|
| Human evidence cited | Four endogenous biomarker/physiology papers; one registered native intervention with no cited result | A naturally occurring SHLP-2 K4R variant was associated with lower Parkinson disease risk; no demonstrated administered-peptide benefit (PMID 38167865) |
| Mechanistic evidence | Mouse metabolic and physical-capacity studies | CXCR7-mediated hypothalamic signaling in experimental models |
| Therapeutic-claim grade | Low | Low for human benefit |
Human MOTS-c studies measured circulating peptide in sleep apnea, diabetes and exercise settings, while administration experiments were in mice. The 2026 physiology study did not find an exercise-related human arterio-venous difference. A 2026 C26 mouse/cell cachexia paper reported partial muscle preservation with preventive exposure, without preserving overall body or fat mass; it is not a human outcome. PMID 40538389 · PMID 40855115 · PMID 41520850 · PMID 42266945
SHLP-2’s 2023 CXCR7 study is a model mechanism. A separate primary study reported that the naturally occurring mitochondrial m.2158 T>C variant, which produces K4R SHLP-2, was associated with lower Parkinson disease risk; its cell and mouse experiments tested mechanisms, not human SHLP-2 treatment. Genotype association is not an administered-peptide result and cannot establish that giving SHLP-2 improves metabolism, protects cells clinically or extends life. CXCR7 model, PMID 37468558 · K4R association, PMID 38167865
NCT07505745 is a native MOTS-c Phase 2 registration with no cited efficacy result. The completed CB4211 registration concerns an analog. Neither record supplies a SHLP-2 or MOTS-c-plus-SHLP-2 outcome.
FDA reports insufficient safety information for compounded MOTS-c products; no combination-safety inference follows from mitochondrial origin. FDA compounding safety review
This selected-source comparison is educational, not use guidance.
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Disclaimer: This comparison is for educational purposes only and does not constitute medical advice. Individual responses to medications vary. Always consult a qualified healthcare provider before making treatment decisions.