PeptideTrace
Research CompoundMitochondrial-Derived Peptide (Preclinical)Metabolic

Humanin (HN, HNG (potent analogue))

C

Evidence Grade C — Moderate human evidence. 521 published studies, 301 human. 2 registered clinical trials.

2 trials521 studiesUSEUCA

Medically reviewed by a licensed medical professional

Overview

Humanin is a peptide encoded in the mitochondrial genome (rather than in nuclear DNA), discovered in 2001 during a search for factors that protect against Alzheimer's-related cell death. It belongs to the emerging field of mitochondrial-derived peptides. No human clinical trials have been conducted. It remains entirely at the preclinical research stage.

Also Known As

Humanin is also known by these brand and alternate names:

Research Activity

521studies
Human 301
Animal 136
In-vitro 113
Reviews 80

521 published studies: 301 human, 136 animal, 113 in-vitro, 80 reviews

Regulatory Status

US
Not approved by FDA(FDA)
EU
Not authorised by EMA(EMA)
CA
Not approved by Health Canada(Health Canada)

Legal Status

USNot applicable (not approved)
EUNot applicable (not authorised)
CANot applicable (not approved)

Summary

Humanin has no marketing authorisation. No human clinical trials have been conducted. The evidence base consists entirely of cell culture and animal studies since its discovery in 2001.

Human observational studies have reported associations between circulating humanin levels and age-related parameters, but observational correlations do not establish therapeutic potential. Like MOTS-c, humanin is of scientific interest within the mitochondrial-derived peptide field but remains at a preclinical stage. No products intended for human use have undergone regulatory review.

Mechanism of Action

Research in cell culture and animal models suggests humanin may interact with multiple signalling pathways including a proposed trimeric receptor complex and anti-apoptotic mechanisms. It was originally identified for its ability to protect neurons from amyloid-beta toxicity in laboratory settings. These observations are entirely preclinical and have not been tested in human trials.

Research Summary

Research in cell culture and animal models suggests humanin may have protective effects against various forms of cellular stress, including amyloid-beta toxicity relevant to Alzheimer's disease. Human observational studies have found correlations between circulating humanin levels and age-related parameters. However, no human clinical trials have been conducted. The evidence consists entirely of preclinical work and observational correlations (which do not establish therapeutic potential). Key concerns include a very short half-life (under 30 minutes), unknown human pharmacology, and a theoretical concern that blocking cell death pathways could promote tumour growth. Modified analogues are under investigation but remain preclinical.

Clinical Trials

PeptideTrace tracks 2 registered clinical trials for Humanin sourced from ClinicalTrials.gov.

NCT06105229N/AUnknown

Clinical Value of Plasma Humanin in Acute Kidney Injury

Guangdong Provincial People's HospitalEndpoint: Humanin concentrationCompletion: 2024-06-01
NCT03431844N/ACompleted

Humanin Isoforms in Cardiac Muscle and Blood Plasma and Major Complications After Cardiac Operation

University of TartuEndpoint: MortalityCompletion: 2019-08-31
View all 2 trials on ClinicalTrials.gov →

Scientific Detail

Overview (Scientific)

Humanin is a 24-amino-acid peptide encoded in mitochondrial 16S rRNA gene. MW ~2,687 Da. First MDP identified (Hashimoto 2001) from Alzheimer's disease functional screen. Plasma ~0.5-1.0 ng/mL, declining with age and in AD. Potent analogue HNG (Ser14Gly) is ~1,000-fold more active. Not approved.

Mechanism of Action (Scientific)

Research suggests multiple pathways: binds CNTFR/WSX-1/gp130 heterotrimeric receptor activating JAK/STAT3; binds IGFBP-3 blocking apoptosis; interacts with BAX preventing mitochondrial translocation and intrinsic apoptosis. Protects against amyloid-beta toxicity, oxidative stress, serum starvation. Improves insulin sensitivity via hypothalamic STAT3.

Summary (Scientific)

No marketing authorization. No human trials. Hashimoto et al. (PNAS 2001): protective against AD neuronal death. Tajima et al. (J Neurosci 2002): HNG rescued memory in AD mice. Muzumdar et al. (2009): improved insulin sensitivity, reduced visceral fat in aged mice. Yen et al. (2020): circulating levels predict longevity across species.

The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.

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Related Compounds

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Guanylate Cyclase-C Agonist

Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.

Elamipretide

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Approved
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Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism. In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.