What Is Colivelin?

Colivelin is a synthetic hybrid neuroprotective peptide designed to combine two distinct survival-peptide systems:

• ADNF-9, a nine-amino-acid fragment of activity-dependent neurotrophic factor
• AGA-(C8R)HNG17, a potent 17-amino-acid Humanin-derived fragment

The two fragments are fused into one continuous 26-residue peptide:

SALLRSIPAPAGASRLLLLTGEIDLP

🧬 Molecular Structure

🧪 Complete amino-acid sequence

Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala-Gly-Ala-Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro

SALLRSIPAPAGASRLLLLTGEIDLP

Hybrid-domain map

Structural characteristics

• 26 standard L-amino acids
• Linear peptide
• No cysteine residues
• No disulfide bonds
• No terminal amidation in the standard reference structure
• Highly hydrophobic leucine-rich central segment
• Two arginine residues contributing positive charge

⚛️ Molecular Weight and 🧫 Formula

Salt forms

Research suppliers may provide Colivelin as a trifluoroacetate or acetate salt. Salt and moisture increase total vial mass without increasing active peptide content, so net peptide content must be reported separately.

📅 Discovery Timeline and Research History

1999–2001: ADNF and Humanin identified

Activity-dependent neurotrophic factor fragments and Humanin were independently recognized as potent neuronal-survival peptides.

2001: Humanin reported

Humanin was identified in a screen for molecules capable of suppressing neuronal death caused by familial Alzheimer’s disease-related insults.

Early 2000s: Potent Humanin analogues developed

Researchers introduced substitutions and truncations that increased Humanin-family potency, including S14G and C8R-related variants.

2005: Colivelin introduced

Colivelin was reported as a fusion of ADNF-9 and AGA-(C8R)HNG17, producing stronger neuroprotection than either component alone in several cellular models.

2006: ALS-model study

Colivelin prolonged survival and improved motor-neuron preservation in G93A-SOD1 transgenic mice.

2008: Nasal treatment in Alzheimer’s models

Intranasal Colivelin improved memory impairment and altered cholinergic activity in mouse models.

2009–2010: Alcohol-related apoptosis research

Colivelin reduced ethanol-induced apoptosis in fetal-brain and neuronal systems.

2010s: Ischemia, retinal, reproductive, and metabolic research

Studies expanded into cerebral ischemia, retinal injury, ovarian function, mitochondrial stress, and systemic cell-survival biology.

2020s: Humanin-family reviews and translational interest

Colivelin remains one of the most potent experimental Humanin-family analogues, but no established phase 1–3 human clinical program has emerged.

ADNF-9 and Humanin Origins

ADNF-9

ADNF-9, also called SALLRSIPA, is a nine-residue fragment derived from activity-dependent neuroprotective protein signaling. It is active at very low concentrations in selected neurotoxicity models.

Humanin

Humanin is a mitochondria-derived peptide associated with cellular stress resistance, metabolism, apoptosis regulation, and neuronal protection.

HNG and C8R modifications

The Humanin portion used in Colivelin incorporates potency-enhancing substitutions associated with S14G-Humanin and C8R-related variants.

AGA truncation

The AGA designation reflects a shortened and modified Humanin-derived fragment retaining a high-potency survival core.

Synergy concept

Colivelin was designed so that one molecule could simultaneously engage ADNF-associated and Humanin-associated survival pathways.

🧠 Proposed Mechanism of Action

Dual-pathway survival signaling

Dominant-negative experiments suggested that both CaMKIV and STAT3 contribute to Colivelin’s rescue effects.

Membrane-receptor signaling

The Humanin family has been associated with a receptor complex involving CNTFRα, WSX-1, and gp130, leading to JAK2 and STAT3 activation.

Intracellular apoptosis proteins

Humanin-family peptides can interact with pro-apoptotic proteins such as BAX, tBID, and IGFBP-3. Direct Colivelin interactions require compound-specific confirmation.

Calcium-regulated signaling

The ADNF-derived region is associated with CaMKIV and calcium-dependent survival pathways.

🎯 Receptor and Pathway Profile

JAK2/STAT3 Signaling

STAT3 activation

Colivelin activates STAT3 in neuronal models, supporting transcription of survival-related genes.

JAK2 involvement

JAK2 lies upstream of STAT3 in the canonical Humanin receptor pathway.

Dominant-negative evidence

Expression of dominant-negative STAT3 reduced Colivelin-mediated rescue, supporting functional involvement.

Survival-gene effects

STAT3 can regulate BCL-2-family proteins, antioxidant defense, inflammation, mitochondrial function, and cell survival.

Context-dependent risk

Persistent STAT3 activation can also support tumor growth, immune evasion, and fibrosis, making chronic safety evaluation essential.

CaMKIV Signaling

ADNF-related pathway

ADNF-derived peptides are associated with calcium/calmodulin-dependent protein kinase signaling.

CaMKIV

CaMKIV regulates neuronal survival, transcription, plasticity, and stress responses.

Dominant-negative evidence

Blocking CaMKIV reduced part of Colivelin’s rescue activity, indicating that the ADNF region remains biologically functional within the hybrid peptide.

Synergistic mechanism

Concurrent CaMKIV and STAT3 activation may explain why Colivelin can outperform its isolated parent fragments in selected assays.

Anti-Apoptotic and Mitochondrial Research

Amyloid-related apoptosis

Colivelin prevented neuronal death caused by amyloid-beta and familial Alzheimer’s disease-related gene insults in cell models.

Mitochondrial injury

Humanin-family signaling can stabilize mitochondria and reduce cytochrome-c release.

Caspase activation

Colivelin reduced downstream caspase-associated apoptosis in several toxin and stress models.

Oxidative stress

Experimental findings suggest improved cellular resistance to reactive oxygen species and metabolic stress.

Survival tradeoff

Preventing apoptosis may protect neurons, but chronic inhibition of cell death could theoretically preserve damaged, senescent, or malignant cells.

Alzheimer’s Disease-Model Research

Familial Alzheimer’s insults

Colivelin suppressed neuronal death induced by mutant amyloid precursor protein and presenilin-associated experimental systems.

Amyloid-beta toxicity

Very low concentrations protected cultured neurons from amyloid-beta-related death.

Memory models

Systemic, intracerebroventricular, and intranasal Colivelin improved memory impairment caused by soluble amyloid-beta or cholinergic disruption in mice.

Synaptic plasticity

Studies reported protection of synaptic function, calcium homeostasis, and memory-related performance.

Amyloid deposition

Some longer-term mouse studies reported reduced pathological changes, although findings remain preclinical and model dependent.

No human Alzheimer’s evidence

Colivelin has not been shown to improve cognition, daily function, amyloid PET, tau biomarkers, or disease progression in people.

Memory and Cholinergic Research

Cholinergic transmission

Intranasal Colivelin altered acetylcholine-related signaling and improved memory in pharmacologically impaired mice.

Scopolamine models

Colivelin reduced memory impairment caused by muscarinic blockade.

Amyloid-induced memory deficits

Behavioral improvement was also reported after soluble amyloid-beta challenge.

Brain access

Behavioral effects after nasal or systemic delivery suggest access to relevant neural pathways, but exact pharmacokinetics remain poorly defined.

No healthy-person nootropic evidence

No controlled human study establishes memory enhancement in healthy individuals.

ALS Research

G93A-SOD1 mice

Colivelin prolonged survival in transgenic mice expressing a familial ALS-associated SOD1 mutation.

Motor-neuron preservation

Histological analysis reported increased spinal motor-neuron survival.

Disease onset and progression

Some functional measures suggested delayed deterioration or improved survival.

Model limitations

SOD1-related ALS represents only a minority of human ALS, and many agents successful in this model have failed clinically.

No human ALS efficacy

Colivelin has not been shown to slow ALS Functional Rating Scale decline, improve respiratory survival, or extend life in patients.

Stroke and Ischemia Research

Cerebral ischemia

Colivelin has been studied in focal and global ischemia models for neuronal survival and functional recovery.

Retinal ischemia

Humanin-family peptides have also been examined in retinal ganglion-cell and ischemic injury models.

Mechanisms

Potential mechanisms include mitochondrial stabilization, STAT3 activation, reduced apoptosis, and anti-inflammatory signaling.

Timing matters

Neuroprotective effects depend heavily on dose, timing, route, reperfusion status, and injury severity.

No emergency treatment role

Colivelin does not replace reperfusion therapy, antiplatelet treatment, blood-pressure management, or rehabilitation.

Alcohol-Related Fetal and Neuronal Injury Research

Fetal-brain apoptosis

Colivelin prevented ethanol-induced apoptosis in fetal mouse brain and cultured neuronal systems.

Oxidative and mitochondrial stress

Ethanol exposure can disrupt mitochondria, increase oxidative stress, and activate caspases; Colivelin reduced selected injury markers.

Developmental implications

The findings generated interest in fetal alcohol spectrum disorder mechanisms.

No prenatal treatment evidence

Colivelin has no established safety in pregnancy and should not be interpreted as protection against alcohol exposure during pregnancy.

Reproductive and Ovarian Research

Ovarian aging

Humanin-family peptides have been studied for follicular survival, ovarian reserve, and age-related reproductive decline.

Granulosa-cell survival

Colivelin may reduce apoptosis in ovarian or reproductive cell models.

Chemotherapy-related injury

Experimental studies have explored whether Humanin analogues protect ovarian tissue during cytotoxic stress.

Potential tradeoff

Protecting normal cells during chemotherapy could theoretically also protect malignant cells, so oncology-specific evaluation is critical.

No fertility treatment evidence

Colivelin has not been shown to improve fertility, live-birth rates, ovarian reserve, or IVF outcomes in humans.

Metabolic and Peripheral Research

Humanin-family metabolic signaling

Humanin analogues can influence insulin sensitivity, glucose regulation, inflammation, and cellular stress responses.

Colivelin-specific evidence

Compared with Humanin and HNG, direct Colivelin metabolic research is more limited.

Cardiovascular and endothelial research

Humanin-family peptides have shown protection in ischemia/reperfusion and vascular models, but compound-specific attribution is necessary.

No metabolic indication

Colivelin is not an approved therapy for diabetes, obesity, cardiovascular disease, mitochondrial disease, or aging.

Brain Delivery and Pharmacokinetic Limitations

Intranasal administration

Intranasal delivery improved memory in mouse models and was intended to bypass some blood–brain barrier limitations.

Systemic administration

Peripheral injections produced central behavioral effects in some studies.

Protease sensitivity

As a 26-residue linear peptide, Colivelin remains vulnerable to enzymatic degradation.

Hydrophobic region

The leucine-rich sequence may affect solubility, aggregation, membrane interactions, and formulation behavior.

No human pharmacokinetics

Absorption, bioavailability, plasma half-life, brain exposure, clearance, metabolism, and active fragments are unknown in humans.

Brain penetrant claim

Animal efficacy suggests functional CNS exposure under some conditions, but it does not establish reliable human brain penetration.

Evidence Limitations and Clinical Interpretation

Preclinical evidence dominates

No established controlled human trial has demonstrated clinical safety or efficacy.

Connected research groups

Much of the foundational work came from closely connected Humanin and ADNF laboratories.

Model concentration

Cell rescue, transgenic ALS mice, amyloid challenge, and toxin models do not reproduce full human disease complexity.

Potency claims vary

Femtomolar potency is highly assay dependent and should not be translated directly into dosing claims.

Mechanism partly inherited

Some receptor and intracellular-target claims are extrapolated from Humanin or ADNF rather than directly demonstrated for Colivelin.

No long-term toxicology

Comprehensive reproductive, developmental, immunogenicity, genotoxicity, carcinogenicity, and chronic-organ safety studies are lacking.

Safety and Regulatory Considerations

No established human safety profile

No approved label defines dosage, route, contraindications, interactions, pregnancy safety, or chronic adverse effects.

Potential neurological risks

• Headache, agitation, or sleep disruption
• Maladaptive survival of injured neurons
• Abnormal plasticity
• Seizure or excitability effects
• Unknown psychiatric effects

Potential proliferative risks

• Persistent STAT3 activation
• Tumor-cell survival
• Immune evasion
• Fibrosis
• Protection of malignant cells from apoptosis

Potential immune and formulation risks

• Immunogenicity
• Aggregation
• Endotoxin contamination
• Residual solvents
• Incorrect salt or peptide content

Pregnancy caution

Despite fetal-neuroprotection research, no human pregnancy safety data exist.

Regulatory status

Colivelin is not FDA approved.

🧪 Laboratory Testing Methods

📄 How to Interpret a Colivelin COA

1. Verify the exact 26-residue sequence: SALLRSIPAPAGASRLLLLTGEIDLP.
2. Confirm hybrid order: ADNF-9 must be N-terminal and the Humanin-derived segment C-terminal.
3. Confirm formula and molecular weight: C₁₁₉H₂₀₆N₃₂O₃₅ and approximately 2,645.1 g/mol.
4. Verify terminal chemistry: The standard reference structure has free peptide termini unless a modified analogue is explicitly intended.
5. Use MS/MS or peptide mapping: HPLC and intact mass alone cannot prove sequence.
6. Review truncations, deletion sequences, leucine/isoleucine assignment, epimers, aggregates, salt content, water, and residual solvents.
7. Measure net peptide content: A “99% purity” result is not the labeled number of milligrams.
8. Require functional testing: STAT3, CaMKIV, or validated neuroprotection assays may support potency.
9. Review proliferation and cytokine data: Routine purity testing does not address chronic STAT3-related risk.
10. Do not infer efficacy: A COA cannot prove Alzheimer’s treatment, ALS survival benefit, brain penetration, memory enhancement, or human safety.

📊 Colivelin vs Humanin vs HNG vs ADNF-9

Colivelin vs P021 vs FGL vs DNSP-11

Colivelin vs Approved Alzheimer’s Care

Colivelin vs Evidence-Based ALS Care

🔗 Related Peptides and Pathways

• Humanin: Parent mitochondrial-derived survival peptide.
• HNG / S14G-Humanin: Potent Humanin analogue.
• ADNF-9: N-terminal component of Colivelin.
• ADNP / NAP: Related activity-dependent neuroprotective peptide system.
• JAK2/STAT3: Humanin-related survival pathway.
• CaMKIV: ADNF-related signaling pathway.
• BAX and tBID: Pro-apoptotic proteins targeted by Humanin-family peptides.
• CNTFRα, WSX-1, and gp130: Proposed Humanin membrane-receptor complex.

🖼️ Original Diagram Specifications

Diagram 1: Colivelin hybrid sequence

Show residues 1–9 as ADNF-9 and residues 10–26 as AGA-(C8R)HNG17, with the fusion junction highlighted.

Diagram 2: Parent-peptide development

Show ADNF → ADNF-9 and Humanin → HNG/C8R fragment → Colivelin.

Diagram 3: Dual signaling model

Show Colivelin activating CaMKIV through the ADNF region and JAK2/STAT3 through the Humanin region.

Diagram 4: Mitochondrial apoptosis

Show amyloid or toxin stress, BAX/tBID, mitochondrial permeabilization, cytochrome-c release, caspases, and Colivelin protection.

Diagram 5: Alzheimer’s-model pathway

Show amyloid-beta, neuronal stress, synaptic dysfunction, cholinergic impairment, and Colivelin-associated rescue.

Diagram 6: Benefit–risk balance

Show neuronal survival and repair on one side and chronic STAT3 activation, tumor survival, fibrosis, and abnormal-cell preservation on the other.

Diagram 7: COA workflow

Show sequence, fusion order, HRMS, MS/MS, amino-acid analysis, aggregation, net content, STAT3/CaMKIV potency, microbiology, and stability.

❓ Frequently Asked Questions

Is Colivelin a peptide?

Yes. It is a synthetic 26-amino-acid hybrid neuroprotective peptide.

What is its exact sequence?

SALLRSIPAPAGASRLLLLTGEIDLP.

What is its molecular formula?

C₁₁₉H₂₀₆N₃₂O₃₅.

What is its molecular weight?

Approximately 2,645.1 g/mol.

What is its CAS number?

867021-83-8 is commonly used.

What is Colivelin made from?

ADNF-9 fused to a potent 17-amino-acid Humanin-derived fragment.

Is Colivelin the same as Humanin?

No. Humanin contributes only the C-terminal region of the hybrid.

What pathways does Colivelin activate?

Its strongest reported pathways are CaMKIV and JAK2/STAT3.

Does Colivelin treat Alzheimer’s disease?

No human therapeutic efficacy has been established.

Does it improve memory?

Mouse studies reported improvements in induced memory impairment. Human evidence is unavailable.

Does Colivelin help ALS?

It prolonged survival in a G93A-SOD1 mouse model, but no human ALS benefit has been established.

Can Colivelin be administered intranasally?

Intranasal administration has been studied in mice, but no approved human protocol exists.

Is Colivelin brain penetrant?

Animal behavioral effects suggest functional CNS exposure under some conditions, but reliable human brain penetration has not been established.

Is Colivelin FDA approved?

No.

Could Colivelin increase cancer risk?

The risk is unknown. Persistent STAT3 and anti-apoptotic signaling could theoretically support tumor-cell survival, and long-term carcinogenicity studies are lacking.

Does 99% HPLC purity prove authentic Colivelin?

No. Complete sequence, fusion order, molecular mass, net content, aggregation, and functional signaling require separate confirmation.

Final Thoughts

Colivelin is a chemically defined 26-residue hybrid peptide engineered to combine ADNF-9 and a high-potency Humanin-derived fragment. Its principal research significance is simultaneous engagement of CaMKIV- and JAK2/STAT3-associated survival pathways.

Preclinical studies report protection against amyloid-related neuronal death, memory impairment, mutant-SOD1 toxicity, ischemia, and alcohol-induced apoptosis. However, no robust human evidence establishes Colivelin as a treatment for Alzheimer’s disease, ALS, stroke, fetal alcohol injury, infertility, or aging.

Legitimate Colivelin material should be verified for its complete sequence, correct fusion order, molecular mass, stereochemical integrity, deletion peptides, aggregation, salt and water content, net peptide amount, STAT3 and CaMKIV pathway activity, route-specific microbiological quality, and stability.

📚 References

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Identity, sequence, hybrid origin, CaMKIV, STAT3, apoptosis, Alzheimer’s, ALS, ischemia, alcohol-injury, reproductive, safety, and analytical evidence were reviewed in July 2026. Colivelin remains an unapproved investigational peptide.