Colivelin [Peptide]

Description

What is Colivelin?

Colivelin (CLN) is a synthetic chimeric neuroprotective peptide developed by Chiba, Yamada, and colleagues at Keio University School of Medicine, Tokyo, first described in 2005. It was designed to potentiate the neuroprotective activity of Humanin (HN) by fusing two established neuroprotective entities: activity-dependent neurotrophic factor (ADNF) — a nine-amino-acid neuroprotective peptide derived from VIP-responsive proteins — is fused to the N-terminus of AGA-(C8R)HNG17, a potent 17-residue C-terminal fragment of the Humanin analogue HNG (S14G-Humanin) in which Cys8 is substituted with Arg8 for enhanced stability. The resulting 26-amino-acid chimeric peptide retains and combines the neuroprotective signalling pathways of both parent components, producing a compound approximately 100-fold more potent than AGA-(C8R)HNG17 alone in isolated neuronal cell preparations.

Colivelin’s neuroprotective activity is mediated through two parallel intracellular signalling cascades: a Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV) pathway triggered by the ADNF component, and a signal transducer and activator of transcription 3 (STAT3) phosphorylation pathway mediated by the Humanin-derived component. The convergence of these two pathways at femtomolar concentrations is proposed as the mechanistic basis for Colivelin’s exceptional potency — it completely suppresses neuronal cell death induced by familial Alzheimer’s disease (FAD) mutant genes and amyloid-beta (Aβ1-43) at concentrations as low as 100 femtomolar (fM) in isolated cell preparations.

Colivelin is not approved by the Food and Drug Administration for human or veterinary use. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic Chimeric Neuroprotective Peptide (ADNF + AGA-(C8R)HNG17 fusion)
Product Name	Colivelin
Application	Scientific / Research Use Only
CAS Number	867021-83-8
Molar Mass	~2651 g/mol (free base)
Chemical Formula	C119H206N32O35
PubChem CID	90477169
Amino Acid Count	26 amino acids
Formal Sequence	H-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-OH
Structural Components	N-terminal ADNF nonapeptide (Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala) fused to AGA-(C8R)HNG17 (C-terminal 17-residue HNG fragment; C8→R8 substitution for stability)
Key Analogues	Humanin (HN, parent 24 AA); HNG (S14G analogue, up to 1000× more potent than HN); AGA-(C8R)HNG17 (17-AA HNG fragment; activity at 10 pM); Colivelin (100-fold more potent than AGA-(C8R)HNG17; activity at 100 fM)
Synonyms	CLN; Colivelin TFA (trifluoroacetate salt form)
Physical Form	Lyophilized white powder; hydrophobic character (DMSO soluble)
Solubility	Soluble in DMSO (100 mg/mL); soluble in water; PBS compatible at working concentrations
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis; COA available per batch)
WADA Status	Not explicitly named on the 2026 WADA Prohibited List. As a non-approved synthetic neuroprotective peptide with documented STAT3 and CaMKIV pathway activity, S0 (Non-Approved Substances) provisions may apply in sport-adjacent research contexts. Verify current status at GlobalDRO.com before use.

How Does Colivelin Work?

Colivelin’s exceptional potency at femtomolar concentrations is proposed to arise from the simultaneous activation of two distinct neuroprotective signalling cascades, each contributed by a different structural component of the chimeric peptide.

CaMKIV Pathway — ADNF Component

The N-terminal ADNF (activity-dependent neurotrophic factor) component of Colivelin triggers Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV) activation in isolated neuronal cell preparations [Chiba et al., 2005]. CaMKIV is a serine/threonine kinase involved in CREB-mediated transcription of pro-survival genes, synaptic plasticity, and anti-apoptotic signalling cascades in neuronal systems. The ADNF nonapeptide is a fragment of VIP-responsive astrocyte-secreted protein; it has independently demonstrated neuroprotective activity in isolated cell preparations. In Colivelin, ADNF’s CaMKIV pathway activation operates additively or synergistically with the STAT3 pathway mediated by the Humanin component, contributing to the ~100-fold potency enhancement over AGA-(C8R)HNG17 alone.

STAT3 Phosphorylation Pathway — Humanin Component

The AGA-(C8R)HNG17 component of Colivelin activates the JAK2/STAT3 signalling axis in isolated neuronal cells and in vivo rodent model preparations, a pathway also characterised for native Humanin and HNG [Yamada et al., 2008]. Colivelin increases STAT3 phosphorylation at Tyr705 in vitro and in vivo in rodent models, and this effect correlates with improvements in working memory performance in Alzheimer’s disease model mice. The STAT3-mediated pathway in Colivelin is also associated with transcriptional upregulation of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) mRNA in neuronal cell preparations, providing a proposed mechanism for Colivelin’s cholinergic system support effects observed in AD model rodent studies [Yamada et al., 2008].

Bax Inhibition and Anti-Apoptotic Activity

The Humanin-derived component of Colivelin retains the Bax-inhibiting anti-apoptotic activity characterised for the parent HN peptide and HNG analogue. In isolated neuronal cell preparations, Colivelin prevents mitochondrial outer membrane permeabilisation and cytochrome c release through inhibition of Bax translocation — a mechanism directly inherited from the AGA-(C8R)HNG17 structural component and linked to the Arg8 substitution, which stabilises the compound against oxidative inactivation at the position corresponding to Cys8 in native Humanin.

Cholinergic Neurotransmission Support

In rodent AD model preparations and isolated neuronal cell systems, Colivelin-mediated STAT3 activation is associated with upregulation of ChAT and VAChT gene expression, markers of cholinergic neuronal function that are characteristically reduced in Alzheimer’s disease pathology. Intranasal administration of Colivelin in rodent AD models transferred the peptide to the CNS via the olfactory bulb and was associated with amelioration of memory impairment, with a proposed mechanism involving STAT3-mediated transcriptional support of cholinergic neurotransmission [Yamada et al., 2008].

Key Research Findings

In preclinical and in vitro research contexts, Colivelin has been associated with the following observations:

• Femtomolar neuroprotection: Colivelin completely suppressed neuronal cell death induced by FAD mutant genes and Aβ1-43 at 100 fM in isolated mouse primary cortical neurons; ~100-fold more potent than parent AGA-(C8R)HNG17 (active at 10 pM); ~50% protection at 10 fM [Chiba et al., 2005].
• Dual pathway neuroprotection: Neuroprotection confirmed to operate via both CaMKIV (ADNF-mediated) and STAT3 (Humanin-derived) pathways simultaneously in isolated neuronal cell preparations; blocking either pathway alone reduces but does not abolish protection [Chiba et al., 2005].
• Intranasal CNS delivery: Intranasally administered Colivelin successfully transferred to the CNS via the olfactory bulb in rodent models; associated with amelioration of memory impairment in anticholinergic-induced and Aβ-induced AD rodent models through STAT3-mediated cholinergic support [Yamada et al., 2008].
• ALS model survival: Colivelin administration prolonged survival in an ALS (SOD1-G93A) transgenic mouse model, improving motor performance — demonstrating neuroprotective activity in a non-AD neurodegenerative disease preclinical model [Chiba et al., 2006].
• Synaptic plasticity and spatial memory: Intrahippocampal Colivelin injection prevented Aβ25-35-induced deficits in spatial learning, memory, hippocampal LTP, and calcium homeostasis in rodent preparations, with effects associated with reduction in neuronal apoptosis and calcium overload.

All findings listed above are derived from preclinical in vitro and in vivo rodent model data. No human clinical trial data have been established for Colivelin. These observations do not constitute evidence of efficacy or safety in any human condition or organism.

What are the Potential Research Applications of Colivelin?

In controlled laboratory environments, Colivelin has been investigated for the following research applications. These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

Ultra-Potent Neuroprotection Pathway Studies Colivelin is employed as the highest-potency Humanin-derived reference compound in studies characterising femtomolar-range neuroprotective signalling in isolated neuronal cell preparations. Research examines dual CaMKIV/STAT3 pathway convergence, minimum effective concentration profiles, and the structural contributions of ADNF and HNG components to combined potency.

STAT3 Pathway Activation and Alzheimer’s Disease Research. In isolated neuronal cell preparations and AD transgenic rodent models (APP/PS1, Tg2576, 3xTg-AD), Colivelin is employed to characterise JAK2/STAT3 axis activation, STAT3 phosphorylation at Tyr705, and downstream transcriptional regulation of neuroprotective and cholinergic markers, including ChAT and VAChT. Research examines the relationship between STAT3 activation and both neuronal survival and cognitive function markers.

Intranasal CNS Peptide Delivery Research Colivelin is employed as a model compound in intranasal-to-CNS delivery pathway research, investigating olfactory bulb-mediated CNS access of neuroprotective peptides. Studies examine transport efficiency, brain distribution following intranasal administration, and the relationship between CNS peptide levels and functional outcomes in rodent AD models.

ALS and Neuromotor Disease Pathway Research. In SOD1-G93A transgenic mouse models of ALS, Colivelin is investigated for motor neuron survival, disease progression markers, and survival duration. Research examines whether STAT3 and CaMKIV pathway engagement provides neuroprotective activity in motor neuron-dominant degenerative models beyond AD-specific pathology.

Chimeric Peptide Design and SAR Studies Colivelin is employed as the primary reference compound in structure-activity relationship investigations examining how ADNF-to-Humanin fusion architecture determines potency, receptor pathway selectivity, and stability. Comparative studies with ADNF, HNG, AGA-(C8R)HNG17, and Colivelin characterise the contribution of each structural element to the chimeric peptide’s activity profile.

What are the Potential Side Effects of Colivelin?

Researchers in preclinical and in vitro settings have noted the following observations. Long-term safety profiles in humans have not been established, and no clinical trial data exist for Colivelin.

• No acute or subacute toxicity to liver or kidney was observed in CD-1 mice following intravenous administration of 200 nmol or intranasal administration of 5 nmol/day for 1 week, as assessed by serum ALT, AST, and creatinine markers [Yamada et al., 2008]
• No adverse effects observed in rodent models at neuroprotective doses in published preclinical studies; no weight loss, motor deficits, or signs of distress reported
• The hydrophobic character of Colivelin may introduce formulation challenges in aqueous biological systems at higher concentrations; aggregation is possible in aqueous media without an appropriate carrier
• STAT3 activator activity: sustained STAT3 phosphorylation in non-target tissues is a theoretical consideration for chronic in vivo administration studies, given STAT3’s roles in cell survival and proliferation across multiple tissue types; not characterised specifically for Colivelin in long-term studies
• No human safety or tolerability data have been established for Colivelin. These observations are derived from rodent experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

Colivelin should only be handled by trained laboratory personnel familiar with synthetic neuropeptide research compounds. Appropriate personal protective equipment is required: nitrile gloves, a laboratory coat, and eye protection at a minimum. When working with lyophilized powder, use within a laminar flow cabinet or a clean area. Avoid aerosol generation during reconstitution. Due to the compound’s hydrophobic character, initial dissolution in DMSO followed by dilution in aqueous buffer is recommended for in vitro assay systems; ensure DMSO final concentration is ≤0.1% in cell-based assays to avoid solvent-mediated cytotoxicity.

Exposure Risks

Risk Tier: LOW

Colivelin has demonstrated a low acute toxicity profile in published rodent preclinical studies at neuroprotective doses. No significant adverse effects have been reported in acute or subacute toxicity assessments in rodent models. The compound’s CNS-active STAT3 and CaMKIV pathway engagement means that inadvertent systemic exposure could produce pharmacological effects in neuronal and non-neuronal tissues expressing these targets, though such effects have not been characterised in humans. No human safety or tolerability data have been established for Colivelin.

Storage

• Lyophilized form: Store at −20°C in original sealed, light-protected container with desiccant
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; peptide integrity may be compromised
• Protect from prolonged light exposure and moisture
• For initial dissolution, DMSO is the recommended primary solvent due to the compound’s hydrophobic character; avoid aqueous-only dissolution of stock solutions at high concentrations

Frequently Asked Questions

Q: What is Colivelin, and what is it investigated for in research? A: Colivelin (CLN) is a synthetic 26-amino acid chimeric neuroprotective peptide comprising ADNF fused to the N-terminus of AGA-(C8R)HNG17 (a Humanin-derived fragment). It is investigated in preclinical and in vitro research contexts for femtomolar-range neuroprotection via dual CaMKIV and STAT3 pathway activation, Alzheimer’s disease neuronal death pathway studies, ALS model motor neuron survival, and intranasal CNS peptide delivery research. It is not approved by the FDA for human use and is intended strictly for laboratory and research purposes.

Q: How does Colivelin relate to Humanin? A: Colivelin is derived from Humanin through a series of optimisation steps. The Humanin sequence was modified to produce HNG (S14G, up to 1000× more potent), then truncated to the active C-terminal 17-residue fragment AGA-(C8R)HNG17 (with Cys8→Arg8 for stability), then fused to the ADNF nonapeptide at the N-terminus to produce Colivelin. Each step increased potency: native Humanin is active at nanomolar concentrations; AGA-(C8R)HNG17 at 10 pM; Colivelin at 100 fM — approximately 100-fold more potent than AGA-(C8R)HNG17 and many orders of magnitude more potent than native Humanin.

Q: What makes Colivelin active at femtomolar concentrations? A: The femtomolar potency is attributed to simultaneous activation of two convergent neuroprotective pathways — CaMKIV (from the ADNF component) and STAT3 (from the AGA-(C8R)HNG17 component) — rather than the potentiation of a single pathway. In isolated cell studies, blocking either pathway alone reduces but does not abolish neuroprotection, suggesting the two pathways contribute additively or synergistically to the combined potency [Chiba et al., 2005].

Q: Has Colivelin been tested for intranasal delivery to the CNS? A: Yes, in rodent preclinical models. Yamada et al. (2008) demonstrated that intranasally administered Colivelin was successfully transferred to the CNS via the olfactory bulb in rodent models and was associated with the amelioration of memory impairment in anticholinergic-induced and Aβ-induced AD mouse models. The proposed mechanism involves STAT3-mediated transcriptional upregulation of ChAT and VAChT — cholinergic neurotransmission markers — in hippocampal and cortical tissues. These are preclinical findings in rodent models; no human intranasal delivery data have been established.

Q: What toxicity observations have been reported for Colivelin in preclinical studies? A: No acute or subacute toxicity to liver or kidney was observed in CD-1 mice following IV administration of 200 nmol or intranasal administration of 5 nmol/day for 1 week, as assessed by standard serum biochemical markers (ALT, AST, creatinine). No adverse effects were reported at neuroprotective doses in published preclinical studies. No human safety or tolerability data have been established for Colivelin.

Q: How should Colivelin be stored and reconstituted? A: Lyophilized Colivelin should be stored at −20°C in a sealed, light-protected container with desiccant. Due to its hydrophobic character, initial dissolution in DMSO (up to 100 mg/mL) is recommended, followed by dilution in aqueous buffer (PBS, cell culture media) to working concentrations. Ensure final DMSO concentration in cell-based assays remains ≤0.1% to avoid solvent cytotoxicity. Reconstituted working solutions should be stored at 4°C and used within 48–72 hours; avoid repeated freeze-thaw cycles.

Related Research Compounds

Researchers investigating Colivelin may also be interested in the following compounds currently available for laboratory research at RCDbio:

• Humanin — The parent mitochondria-derived 24-amino acid peptide from which Colivelin is ultimately derived; provides the foundational Bax-inhibition and STAT3 activation mechanistic reference for Colivelin’s Humanin-component activity.
• N-Acetyl-Selank — A synthetic neuropeptide investigated for BDNF upregulation and GABAergic pathway modulation; shares the CNS neuroprotective signalling research context with Colivelin in comparative neuropeptide pharmacology studies.

All products listed are for laboratory and research purposes only.

References

1. Chiba, T., Yamada, M., Hashimoto, Y., Sato, M., Sasabe, J., Kita, Y., Terashita, K., Aiso, S., Nishimoto, I., & Matsuoka, M. (2005). Development of a femtomolar-acting humanin derivative named colivelin by attaching activity-dependent neurotrophic factor to its N terminus: characterization of colivelin-mediated neuroprotection against Alzheimer’s disease-relevant insults in vitro and in vivo. Journal of Neuroscience, 25(44), 10252–10261. https://pubmed.ncbi.nlm.nih.gov/16267233/

2. Yamada, M., Chiba, T., Sasabe, J., Terashita, K., Aiso, S., & Matsuoka, M. (2008). Nasal colivelin treatment ameliorates memory impairment related to Alzheimer’s disease. Neuropsychopharmacology, 33(8), 2020–2032. https://pubmed.ncbi.nlm.nih.gov/17928813/

3. Chiba, T., Yamada, M., Sasabe, J., Terashita, K., Aiso, S., & Matsuoka, M. (2006). Colivelin prolongs the survival of an ALS model mouse. Biochemical and Biophysical Research Communications, 343(3), 793–798. https://pubmed.ncbi.nlm.nih.gov/16564029/

4. Wu, M. N., Zhou, L. W., Wang, Z. J., Han, W. N., Zhang, J., Liu, X. J., Tong, J. Q., & Qi, J. S. (2015). Colivelin ameliorates amyloid β peptide-induced impairments in spatial memory, synaptic plasticity, and calcium homeostasis in rats. Hippocampus, 25(3), 363–372. https://pubmed.ncbi.nlm.nih.gov/25332198/ 

Disclaimer

Colivelin is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

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