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| 1mg |
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| Targets |
Humanin acts through multiple targets, including the formyl peptide receptor-like-1 (FPRL1) and the ciliary neurotrophic factor receptor (CNTFR). Humanin also directly binds to BCL2-associated X protein (BAX), a pro-apoptotic protein, preventing its translocation to mitochondria and subsequent cytochrome c release. The peptide exhibits cytoprotective, anti-apoptotic, and neuroprotective activities. (Gly14)-Humanin is an analog with preserved or enhanced activity.
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| ln Vitro |
(Gly14)-Humanin (human) acetate (0.1–10 μM; 72 hours) markedly reduced ROS production, bax/bcl-2 ratio, cleaved PARP levels, and HUVEC nuclear fluorescence while increasing cell survival. Moreover, the mRNA levels of bcl-2 and bax are increased and decreased, respectively [1].
In vitro, Humanin and its analogs including (Gly14)-Humanin protect multiple cell types from cell death induced by various insults. In neuronal cell lines (e.g., PC12 cells, primary cortical neurons) treated with the Alzheimer's amyloid-beta peptide (Abeta1-42, 10-50 uM), (Gly14)-Humanin (0.1-10 uM) significantly increases cell viability and reduces apoptotic markers. The peptide suppresses cytochrome c release from mitochondria, reduces caspase-3 activation, and prevents DNA fragmentation. The EC50 for neuroprotection is typically in the low nanomolar to picomolar range. |
| ln Vivo |
(Gly14)-Humanin (human) acetate (0.1 μg/5 μL; icv; once) decreases the amount of brain injuries, enhances motor function, and improves Morris water performance in the maze test in damaged cortex and hippocampus [2].
In vivo, Humanin and its analogs have shown therapeutic efficacy in animal models of Alzheimer's disease, stroke, and other neurodegenerative conditions. In APP/PS1 transgenic mouse models of Alzheimer's disease (which overproduce amyloid-beta), chronic administration of (Gly14)-Humanin reduces Abeta deposition in the brain, improves cognitive function in the Morris water maze, and reduces neuroinflammation. The peptide also reduces ischemic brain damage in middle cerebral artery occlusion (MCAO) models of stroke. (Gly14)-Humanin is one of the more potent analogs studied. |
| Enzyme Assay |
For receptor binding assays, membranes from HEK293 cells expressing FPRL1 or CNTFR are incubated with radiolabeled Humanin or (Gly14)-Humanin with varying concentrations of unlabeled test peptide. After incubation at 25degC for 60-90 minutes, bound and free ligand are separated by filtration. For BAX binding, surface plasmon resonance (SPR) is performed using immobilized recombinant BAX protein. (Gly14)-Humanin is injected at varying concentrations, and the binding affinity (Kd) is calculated.
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| Cell Assay |
For neuroprotection assays, mouse primary cortical neurons or human SH-SY5Y neuroblastoma cells are seeded in 96-well plates. Cells are pre-treated with (Gly14)-Humanin (0.1 pM to 1 uM) for 1-2 hours, then exposed to neurotoxic stimuli: Abeta1-42 oligomers (10-50 uM), staurosporine (0.1-1 uM), or oxygen-glucose deprivation (OGD) for in vitro ischemia. After 24-48 hours, cell viability is measured by MTT, CCK-8, or calcein-AM staining. Apoptosis is assessed by caspase-3/7 activity, TUNEL staining, or Annexin V/PI flow cytometry. Cytochrome c release from mitochondria is detected by Western blot of cytosolic vs. mitochondrial fractions.
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| Animal Protocol |
For the Alzheimer's disease model, male APP/PS1 transgenic mice (6-12 months old) are used. (Gly14)-Humanin is administered via intracerebroventricular (ICV) injection (1-10 ug/mouse) or intraperitoneally (IP, 0.5-5 mg/kg) daily for 4-8 weeks. Cognitive function is assessed by Morris water maze (escape latency, probe trial) or novel object recognition. After behavioral testing, brains are collected for biochemical analyses: Abeta1-42/1-40 levels by ELISA, amyloid plaque burden by immunohistochemistry (6E10 antibody), and neuroinflammation by Iba-1 (microglia) and GFAP (astrocytes) staining. For stroke models, MCAO is performed, and infarct volume is measured by TTC staining.
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| ADME/Pharmacokinetics |
As a 24-amino acid peptide, Humanin and its analogs have low oral bioavailability and short plasma half-lives (typically 10-30 minutes) due to rapid proteolytic degradation and renal clearance. For in vivo studies, peptides are typically administered via intraperitoneal (IP), intravenous (IV), or intracerebroventricular (ICV) routes. Some stable analogs of Humanin (e.g., HNG, AG, or S14G-Humanin) have been developed with improved stability and bioavailability. The acetate salt form improves water solubility.
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| Toxicity/Toxicokinetics |
As an endogenous peptide with cytoprotective activity, Humanin and its analogs are generally well-tolerated in preclinical studies. Even at high doses (up to 10 mg/kg in mice), no overt signs of toxicity, including body weight loss, abnormal behavior, or organ toxicity, have been observed. Humanin is produced naturally in the body, so it is not considered foreign or immunogenic. No significant hepatotoxicity, nephrotoxicity, or genotoxicity has been reported. This favorable safety profile supports the potential therapeutic development of Humanin analogs.
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| References |
[1]. Ying Xie, et al. Protection effect of [Gly14]-Humanin from apoptosis induced by high glucose in human umbilical vein endothelial cells. Diabetes Res Clin Pract. 2014 Dec;106(3):560-6.
[2]. T Wang, et al. [Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice. Neuroscience. 2013 Feb 12;231:70-81. |
| Additional Infomation |
Humanin was discovered in 2001 as a neuroprotective factor against Alzheimer's disease insults. It is encoded by the mitochondrial genome (MT-RNR2) and is the first identified member of the mitochondrial-derived peptides (MDPs) family. Multiple Humanin analogs have been developed with improved potency and stability, including (Gly14)-Humanin, AGA-(HNG)-Humanin, and S14G-Humanin. Humanin analogs have been studied in preclinical models of Alzheimer's disease, stroke, myocardial infarction, diabetes, and other diseases. This product is for research use only and is not FDA-approved for human therapy.
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| Molecular Formula |
C118H202N34O31S2.XC2H4O2
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| Molecular Weight |
2657.21 (free acid)
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| Related CAS # |
(Gly14)-Humanin (human);330936-70-4
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~50 mg/mL
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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