RESEARCH MONOGRAPH · KDC-MN-1345

Humanin

May 9, 2026 Kodiac biolabs Research Revised May 19, 2026 2 min read

Our opinion on this compound

63/100

The mitochondrial-derived peptide story is real, humanin is the prototype, and we're still mostly in early innings

Humanin was the first mitochondrial-derived peptide (MDP) identified and remains the prototype for the whole class. Pinchas Cohen's group at USC discovered it in the early 2000s while looking for neuroprotective factors against Alzheimer's-associated apoptosis, and the story that's unfolded since is that mitochondria don't just make ATP, they secrete signaling peptides encoded in the mitochondrial genome itself. That's a conceptual shift that took the field a while to absorb.

The 24-residue peptide signals primarily through a tripartite receptor complex including FPR2, CNTFR, gp130, and WSX1, and the downstream effects include STAT3 activation, anti-apoptotic signaling, and metabolic modulation in multiple tissues. Plasma humanin levels decrease with age and correlate with various age-related disease states, which is the kind of correlation that's suggestive but doesn't prove causality.

What we like about humanin: the underlying biology (mitochondria as endocrine organs producing peptide signals) is genuinely interesting and is being validated by the discovery of additional MDPs like MOTS-c, the SHLPs, and gau peptides. As a research tool for studying mitochondrial-nuclear retrograde signaling, humanin is the foundational compound.

Where we hedge: most of the strong data is preclinical. There's neuroprotection in Alzheimer's models, cardioprotection in ischemia-reperfusion models, anti-apoptotic effects in beta cells and various stress paradigms, but the human translation work is thin. A handful of small studies looking at humanin levels in disease cohorts, basically no interventional trials with exogenous humanin. The pharmacology in humans is largely uncharacterized.

The analog issue matters here. Native humanin has a short half-life. Most preclinical work uses analogs like HNG (S14G-humanin) that are 1000x more potent, and some vendors sell HNG as humanin which is technically a different molecule. Verify what you're getting.

Sourcing for native 24-residue humanin is reasonable, standard SPPS, HPLC verification straightforward. For the modified analogs, the substitution sites matter and good vendors will show you sequence verification by mass spec.

Honestly the MDP field is one of the more interesting areas of mitochondrial biology right now and humanin is the entry point. dont expect clinical translation soon, but as a probe for retrograde mitochondrial signaling it's a serious tool.

Evidence: 45
Mechanism: 70
Reliability: 60
Safety: 72
Sourcing: 70
Value: 60
Signal: 60
Staying power: 70

24-residue mitochondrial-derived peptide (MDP)

A 24-amino-acid peptide encoded within the 16S rRNA of the mitochondrial genome, identified as a neuroprotective and metabolic factor with broad anti-apoptotic activity.

Abstract

Humanin (Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala; molecular weight 2687.27 free peptide; CAS 330936-69-1) is a 24-residue peptide encoded within the 16S ribosomal RNA gene of the mitochondrial genome, identified by Yuichi Hashimoto and colleagues at Keio University in 2001 in a screen for anti-apoptotic factors that protected against amyloid-beta-induced neuronal death. Humanin is the founding member of the mitochondrial-derived peptide (MDP) family, a class of peptides encoded within mitochondrial DNA and translated from short open reading frames in mitochondrial RNAs; other family members include MOTS-c (KDC-MN-008), the SHLP family (small humanin-like peptides 1 through 6), and gau (gene antisense ubiquitous). The pharmacological signature of humanin includes anti-apoptotic activity through binding the BAX and BIM Bcl-2 family pro-apoptotic proteins, suppression of caspase activation, neuroprotection against amyloid-beta, prion peptide, and ALS-associated SOD1 toxicity in rodent and cell culture models, modulation of metabolic phenotypes (improved insulin sensitivity in rodent obesity models), and cytoprotection in models of myocardial ischemia and chemotherapy-induced toxicity. Receptors include the heterotrimeric ciliary neurotrophic factor (CNTF) receptor complex (CNTFR-WSX-1-gp130), the formyl peptide receptor 2 (FPR2), and direct cytoplasmic protein-protein interactions with BAX/BIM. The S14G analog of humanin (HNG; gly substituted for ser at position 14) is approximately 1000-fold more potent in neuroprotection assays and is the principal research-grade analog used in pharmacology studies. The compound is research-grade with no regulatory approval; clinical development has been limited despite the strong preclinical signal, attributed in part to the narrow therapeutic window for neurodegenerative disease drugs and the sparse human pharmacokinetic characterization.

Mechanism of action

Anti-apoptotic through binding BAX and BIM. Receptor binding at CNTFR-WSX-1-gp130 trimer and FPR2. Suppression of caspase activation. Neuroprotection, metabolic improvement, and cytoprotection across multiple injury models.

Reported research dose ranges

Rodent and research-grade dosing 0.5 to 5 mg/kg intraperitoneal or subcutaneous. The S14G analog is used at proportionally lower doses.

References

Hashimoto Y, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes. Proc Natl Acad Sci USA 2001.
Cohen P, et al. Mitochondrially encoded peptides as a new class of metabolic regulators. Cell Metab 2014.
Lee C, et al. Humanin: a harbinger of mitochondrial-derived peptides. Trends Endocrinol Metab 2013.

Read the full monograph

The full reference document is available below as a PDF embed and download. Note: PDFs for newly added compounds may take a few hours to propagate after this article was published.

KDC-MN-1345 Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Humanin

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

Quick actions

Categories

Help and policies

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

Adjacent monographs