HNG (Humanin-Gly, S14G-Humanin) — Safety, Research, Risks & Legal Status

Not medical advice. HNG (Humanin-Gly, S14G-Humanin) is discussed here for informational and harm-reduction purposes only. We do not endorse use, and any dosing context is informational, not a protocol.

Also known as	S14G-Humanin, Gly14-Humanin, (Gly14)-Humanin, HNG peptide
Category	Peptide (research chemical)
Origin	Synthetic analog of humanin, a 24-amino acid peptide encoded within the mitochondrial 16S rRNA locus
Potency vs. wild-type	Approximately 1,000-fold more potent than native humanin in cell-based neuroprotection assays (preclinical)
Key substitution	Serine-to-glycine at position 14 (S14G); single amino acid change accounts for potency increase
Development stage	Strictly preclinical as of July 2026; no completed or active Phase I human trials on ClinicalTrials.gov
Availability	Sold as a laboratory research reagent by Sigma-Aldrich (H6161), Enzo Life Sciences, and Eurogentec; no GMP pharmaceutical formulation
Primary model systems	Transgenic Alzheimer's mouse lines, murine cardiac ischemia models, stroke models, asthma and gouty arthritis mouse models
US legal status	Not FDA-approved for any indication. No Investigational New Drug (IND) application identified in public records as of mid-2026. Available commercially only as a laboratory research reagent not intended for human use. Status is the same in the EU and elsewhere - no regulatory approval or clinical development designation has been identified globally. Purchasing or administering this compound for human use falls outside any sanctioned legal framework in the United States.

What is HNG (Humanin-Gly, S14G-Humanin)?

HNG (also called S14G-Humanin or Gly14-Humanin) is a synthetic analog of humanin, a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA region of the mitochondrial genome. The analog contains a single serine-to-glycine substitution at position 14, which confers approximately 1,000-fold greater potency than wild-type humanin in cell-based neuroprotection assays. It is currently available only as an academic research reagent and has not entered human clinical trials.

How it works

HNG activates the PI3K/Akt cell-survival signaling pathway and modulates apoptotic balance by suppressing the pro-apoptotic protein BAX while upregulating BCL-2. It also inhibits inflammatory cascades including the TLR4/NF-kB axis and TGF-beta/Smad2/3 fibrosis pathways, reduces reactive oxygen species (ROS) production, and suppresses MAPK family protein activation. Additionally, preclinical data suggest chaperone-like activity: HNG has been shown to block amyloid misfolding and seeding (including IAPP aggregation) at substoichiometric concentrations in cell-free and cell-based models. No validated human pharmacokinetic or pharmacodynamic data exist.

Background & history

Native humanin was first described in the early 2000s by Nishimoto and colleagues, who identified it encoded within a mitochondrial genomic locus while screening for factors capable of rescuing neurons from Alzheimer's-disease-related cell death. The S14G substitution was subsequently characterized as producing markedly enhanced potency, establishing HNG as the preferred tool compound for research into humanin biology. The peptide's development has remained almost entirely within academic and institutional gerontology and neuroscience research programs; no single pharmaceutical or biotechnology company has claimed primary development rights. It is sold as a licensed reagent by Sigma-Aldrich, Enzo Life Sciences, and Eurogentec, among others.

What the research says

All available evidence is preclinical as of July 2026. Animal models (primarily mouse, including transgenic Alzheimer's lines) have demonstrated neuroprotective, cardioprotective, and anti-inflammatory effects. Cardiac stress models and stroke models have shown reduced infarct size and improved survival metrics. Asthma and gouty arthritis mouse models showed attenuation of inflammatory endpoints. HNG's approximately 1,000-fold potency advantage over wild-type humanin is consistently observed in cell-based neuroprotection assays. No completed or active Phase I human trials are registered on ClinicalTrials.gov as of mid-2026. No human pharmacokinetic data are available. No human efficacy or safety signals (positive or negative) can be drawn from the existing literature.

Reported effects

Neuroprotection in rodent Alzheimer's and stroke models (preclinical only)
Cardioprotection in murine cardiac stress and ischemia-reperfusion models (preclinical only)
Anti-apoptotic activity via PI3K/Akt and BCL-2 upregulation (in vitro and animal data only)
Anti-inflammatory effects across TLR4/NF-kB and TGF-beta pathways in animal models
Suppression of amyloid/IAPP misfolding and seeding at substoichiometric concentrations (in vitro)
Attenuation of inflammatory endpoints in asthma and gouty arthritis mouse models (preclinical only)
Reduction of reactive oxygen species production in cell and animal models

Dosing & administration (informational)

Literature ranges referenced in preclinical studies are not translatable to human use given the complete absence of human pharmacokinetic data. Published animal study doses span a wide range and vary by route of administration, model system, and endpoint. This information is provided for academic reference only and does not constitute a protocol or recommendation. Any use of this compound in humans would require independent IND authorization and institutional oversight. Consult a clinician or regulatory affairs specialist before any consideration of investigational use.

This is general research/context information, not medical advice or a recommended protocol.

Safety & side effects

No human safety data exist; all safety observations derive from animal studies
No serious adverse events reported in published animal studies at tested doses; IV infusion alone showed no observable toxicity signal in mice
Theoretical concern: anti-apoptotic mechanism could impair tumor surveillance and promote cancer progression; this has not materialized as a consistent signal in available preclinical models and some studies suggest anti-tumor activity in certain contexts, but long-term oncological safety in humans is entirely unknown
Long-term human safety data are absent; chronic use risk profile is undefined
Presumed investigational side effects extrapolated from structural analogs: injection-site irritation, transient headache, fatigue, nausea - none formally documented in clinical populations
No pharmacokinetic data in humans (absorption, distribution, metabolism, excretion, half-life) are available to guide any dosing or safety assessment

Drug & supplement interactions

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Who should avoid it

Any human use outside an IRB- and IND-authorized clinical trial setting
Use in individuals with active or prior malignancy given theoretical anti-apoptotic tumor surveillance concerns
Combination with chemotherapy or other pro-apoptotic agents without formal study
Gray-market or unverified peptide sources lacking analytical certificates
Use in pregnancy or lactation (no reproductive safety data exist)
Extrapolating animal dosing directly to human use

How it is commonly combined

No evidence-based stacking data exist for HNG. Any combination with other research peptides, mitochondrial-targeted compounds, or anti-aging agents is entirely speculative and uncharacterized from a safety or pharmacological standpoint. The compound has not been studied in combination contexts in human subjects.

Legal & regulatory. Not FDA-approved for any indication. No Investigational New Drug (IND) application identified in public records as of mid-2026. Available commercially only as a laboratory research reagent not intended for human use. Status is the same in the EU and elsewhere - no regulatory approval or clinical development designation has been identified globally. Purchasing or administering this compound for human use falls outside any sanctioned legal framework in the United States.

Quality & harm reduction

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Find HNG (Humanin-Gly, S14G-Humanin) →

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Frequently asked questions

Is HNG the same as humanin?

No. HNG (S14G-Humanin) is a synthetic analog of native humanin with a single amino acid substitution (serine to glycine at position 14). This change confers approximately 1,000-fold greater potency in preclinical neuroprotection assays. Wild-type humanin and HNG share the same mechanistic pathways but differ meaningfully in biological activity at equivalent concentrations.

Has HNG been tested in humans?

No. As of mid-2026, no completed or active human trials appear on ClinicalTrials.gov for S14G-humanin or HNG. All efficacy and safety data are derived from cell-based and animal studies. No human pharmacokinetic, pharmacodynamic, safety, or efficacy data are available.

What is the recommended dose?

There is no established or recommended human dose. HNG has not entered human clinical trials, and animal study doses cannot be reliably extrapolated to humans without pharmacokinetic bridging studies. Any dosing question should be directed to a licensed clinician or research physician - this entry does not and cannot provide a protocol.

Is the anti-apoptotic mechanism a cancer risk?

This is a legitimate theoretical concern. HNG suppresses BAX and upregulates BCL-2, which are mechanisms that in principle could impair the clearance of pre-malignant cells. However, this has not produced a consistent oncogenic signal in published animal models, and some preclinical studies have reported anti-tumor activity in specific cancer contexts. Long-term oncological safety in humans is entirely unknown and cannot be assessed from existing data.

Where can I obtain research-grade HNG?

HNG is sold as a laboratory research reagent by Sigma-Aldrich (catalog H6161), Enzo Life Sciences, and Eurogentec, among other life science suppliers. These are intended for in vitro and animal research use only, not for human administration. Purchase from gray-market or unverified peptide vendors carries significant risks of impurity, inaccurate concentration, and contamination.

What is HNG's legal status in the United States?

HNG is not FDA-approved for any therapeutic indication and no Investigational New Drug application has been publicly identified. It is not a scheduled substance under the Controlled Substances Act, but administering it to humans outside an authorized clinical trial would fall outside any sanctioned regulatory framework. It may be purchased and possessed for legitimate laboratory research purposes.

References & further reading

PubMed: "S14G-humanin neuroprotective" OR "S14G-humanin cardioprotective"
PubMed: "mitochondrial-derived peptides humanin analog" OR "humanin S14G potency"
PubMed: "humanin IAPP chaperone" OR "mitochondrial peptide amyloid"
ClinicalTrials.gov: search term "humanin" (no active or completed trials for S14G-HNG as of mid-2026)
Alzheimer's Drug Discovery Foundation Cognitive Vitality: "Humanin and Humanin Analogs" (alzdiscovery.org cognitive vitality reports)