Description
Disclaimer: HNG ([Gly14]-Humanin) is not approved by the U.S. Food and Drug Administration (FDA) for human or veterinary use. It is intended strictly for laboratory and research purposes only.
What is HNG ([Gly14]-Humanin)?
HNG is a synthetic analog of Humanin (HN). It is the first identified mitochondria-derived peptide (MDP). Humanin is a 24-amino acid peptide encoded within the 16S ribosomal RNA region of human mitochondrial DNA (mtDNA). HNG is generated through a single amino acid substitution at position 14, where serine (S) is replaced by glycine (G), producing the modified sequence MAPRGFSCLLLLTGEIDLPVKRRA.
HNG belongs to the family of mitochondria-derived peptides (MDPs) and is classified in research literature as a humanin analog. The S14G substitution is associated with up to 1000-fold greater cytoprotective potency than native humanin in preclinical assay models. It is studied in laboratory settings in the context of neuroprotection, metabolic signaling, and apoptosis regulation. HNG is not an approved therapeutic compound and is intended exclusively for qualified researchers in controlled laboratory environments.
PROPERTIES OF HNG
| Property | Details |
| CAS Number | 330936-70-4 |
| Molar Mass | 2657.3 Da |
| Chemical Formula | C118H202N34O31S2 |
| Stability/ Shelf life | 24 months when stored lyophilized at −20 °C under recommended conditions. |
| Synonyms | [Gly14]-HN, Humanin-G, sHNG, HNG, [Gly14]-Humanin (Human) |
| Storage Instructions | −20 °C (lyophilized); protect from light, heat, and moisture |
| Amino Acid Sequence | Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala |
| Wada Status | Not explicitly listed on the WADA 2026 Prohibited List |
WORKING MECHANISM OF HNG
HNG is thought to act through the GP130/IL6ST (gp130) cell-surface receptor complex in experimental models. Binding to this complex is associated with downstream activation of multiple intracellular signaling cascades. Based on articles retrieved from PubMed, these include the AKT (protein kinase B), ERK1/2 (extracellular signal-regulated kinase), and STAT3 (signal transducer and activator of transcription 3) pathways.
Mechanistically, HNG is thought to influence:
- cAMP-independent pro-survival signaling via STAT3 modulation in neuronal cell culture models
- PI3K/AKT pathway activity, observed in granulosa cell models evaluating insulin receptor signaling
- Caspase-3 downregulation, associated with reduced apoptotic activity in Aβ-exposed hippocampal rat models
- Inhibition of IGFBP3–Importin-β1 interaction, a molecular mechanism through which HN analogs are studied in relation to nuclear translocation and apoptosis regulation.
The S14G substitution is associated with increased resistance to enzymatic degradation relative to native Humanin. However, HNG remains susceptible to oxidation and dimerization in aqueous solutions, which must be accounted for in experimental design. Receptor pharmacology data in human systems remain limited. All mechanistic findings are derived from in vitro and animal-based research models only.
What are the Potential Research Observations of HNG Peptide?
The following research findings are based on articles retrieved from PubMed and are reported from preclinical and in vitro studies only. These findings do not constitute clinical evidence.
Neuroprotective Observations in Amyloid-β Preclinical Models
[Gly14]-Humanin has been investigated for its interactions with Aβ-induced neurotoxicity in rat models. Intrahippocampal administration of Aβ fragments was associated with impaired spatial learning and memory, along with upregulation of caspase-3 and downregulation of STAT3. Pretreatment with HNG was associated with preservation of STAT3 expression and attenuation of memory disruption. Findings are from a rat experimental model and have not been replicated in human clinical studies.
Signaling Pathway Activation in Age-Related Research Models
HNG has been studied in relation to ERK1/2, AKT, and STAT3 pathways via the GP130/IL6ST receptor complex. In aged mice, hippocampal AKT and ERK1/2 phosphorylation increased following administration, an effect not observed in younger mice. This suggests an age-dependent variable in the compound’s signaling profile. Significance in human biology remains unclear.
Brain Mitochondrial Function in Cardiac Ischemia-Reperfusion Models
HNG was studied in a rat model of cardiac ischemia-reperfusion (I/R) injury. Administration was associated with attenuation of brain mitochondrial dysfunction, reduced tau hyperphosphorylation, and decreased amyloid-β accumulation in preclinical brain tissue. No significant effect on blood-brain barrier integrity or oxidative stress markers was observed. Findings are from a Wistar rat model and require further validation. [Kumfu et al., 2018 examined native Humanin in this model; HNG’s enhanced potency profile makes it a relevant candidate tool compound for analogous cardiac I/R research models]
Note: HNG ([Gly14]-Humanin) is not approved by the U.S. Food and Drug Administration (FDA) for human or veterinary use. It has no approved therapeutic indications. This compound is intended strictly for scientific research purposes only.
Safety Profile and Toxicological Considerations
Researchers have noted the following observations in experimental settings. Long-term safety data remain absent, and a complete toxicity profile has not been established in any biological system.
- HNG is susceptible to rapid oxidation and dimerization in aqueous solutions, affecting experimental reliability
- No LD50 or chronic toxicity data are available in peer-reviewed literature
- Inadvertent exposure risks are not established; no human safety profile exists
- Repeated freeze-thaw cycles are associated with reduced peptide integrity
- Receptor pharmacology data in human systems remain limited and inconclusive
- Potential interference with intracellular signaling cascades outside of targeted experimental pathways
WHY CHOOSE RCDBIO FOR HNG?
Each batch of HNG ([Gly14]-Humanin) supplied by RCDbio undergoes independent third-party laboratory testing, with a batch-specific Certificate of Analysis (COA) available for researcher verification before experimental use.
- Independent third-party laboratory testing per batch
- COA confirming compound identity and purity per lot
- Molecular identity confirmed against CAS 330936-70-4
- RCDbio does not self-certify; all quality verification is conducted by accredited independent laboratories
Disclosure: Sponsored by RCDbio. This content is for informational purposes only and does not constitute an endorsement of any product for human use.
FREQUENTLY ASKED QUESTIONS
Is HNG approved for human use?
No. HNG ([Gly14]-Humanin) is not approved by the FDA for any human or medical application. It is classified as a research-use peptide only and has no approved therapeutic indications in the United States or any other regulatory jurisdiction.
What is the structural difference between HNG and native Humanin?
HNG is generated through a single amino acid substitution at position 14 of the native Humanin sequence, where serine (S) is replaced by glycine (G). This S14G modification is associated with substantially increased cytoprotective potency in preclinical models compared to the unmodified Humanin sequence.
What receptor complex is HNG thought to interact with in research models?
Based on articles retrieved from PubMed, HNG is thought to interact with the GP130/IL6ST (gp130) receptor complex in experimental models. This interaction is proposed to activate downstream signaling pathways, including AKT, ERK1/2, and STAT3. These findings are from preclinical models only.
How should HNG be stored in a laboratory setting?
Lyophilized HNG should be stored at −20 °C in a dry, dark environment, away from heat, moisture, and light. Reconstituted peptide solutions are highly susceptible to oxidation and dimerization and should be used promptly following validated laboratory protocols. Stability data should inform experimental design when using HNG in solution.
What is the significance of HNG’s susceptibility to oxidation and dimerization in laboratory settings?
HNG ([Gly14]-Humanin) is highly susceptible to oxidation and dimerization in aqueous solutions. These processes alter the peptide’s structural integrity and can compromise experimental reproducibility. Researchers should reconstitute immediately before use, aliquot before
freezing, avoid repeated freeze-thaw cycles, and account for stability limitations when designing experimental protocols and interpreting results.
REFERENCES
Kim, S.-J., Guerrero, N., Wassef, G., Xiao, J., Mehta, H. H., Cohen, P., & Yen, K. (2016). The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus. Oncotarget, 7(30), 46899–46912. https://doi.org/10.18632/oncotarget.10380
Sreekumar, P. G., Mishra, A., Bhootada, Y., Reddy, G. B., Bhatt, S., & Kannan, R. (2023). Stability Determination of Intact Humanin-G with Characterizations of Oxidation and Dimerization Patterns. Biomolecules, 13(3), 515. https://doi.org/10.3390/biom13030515
Yuan, L., Liu, X.-J., Han, W.-N., Li, Q.-S., Wang, Z.-J., Wu, M.-N., Yang, W., & Qi, J.-S. (2016). [Gly14]-Humanin Protects Against Amyloid β Peptide-Induced Impairment of Spatial Learning and Memory in Rats. Neuroscience Bulletin, 32(4), 374–382. https://doi.org/10.1007/s12264-016-0041-x
Sirinart Kumfu, Charununtakorn, S. T., Thidarat Jaiwongkam, Nipon Chattipakorn, & Chattipakorn, S. C. (2018). Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury. Journal of Alzheimer’s Disease, 61(4), 1343–1353. https://doi.org/10.3233/jad-170708
Disclaimer
HNG ([Gly14]-Humanin) is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition. The Food and Drug Administration has not evaluated the statements on this page. Researchers must comply with all applicable local laws and regulations governing the use of research compounds. By purchasing, you agree to RCDbio Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.
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