Overview
CAQK is a tetrapeptide consisting of just four amino acids: cysteine, alanine, glutamine, and lysine. First identified in 2016 through in vivo phage display screening in mice with acute brain injury, CAQK has emerged as a promising candidate for treating traumatic brain injury (TBI)—a condition with no currently approved drug treatments.
What makes CAQK remarkable is its ability to specifically home to damaged brain tissue when administered intravenously, accumulating precisely where it's needed while largely bypassing healthy tissue.
Molecular Characteristics
CAQK is defined by the following molecular properties:
| Property | Value |
|---|---|
| Sequence | Cys-Ala-Gln-Lys |
| Molecular Formula | C₁₇H₃₂N₆O₆S |
| Molecular Weight | 448.54 Da |
| CAS Number | 2088281-24-5 |
| Type | Tetrapeptide |
The peptide's simple four-amino-acid structure offers significant advantages for drug development: it is easy to synthesize at scale, demonstrates good tissue penetration, and is non-immunogenic.
Mechanism of Action
CAQK's targeting capability relies on its specific binding to components of the extracellular matrix that become upregulated following brain injury:
Primary Target: Tenascin-C
Tenascin-C is an extracellular matrix protein that is absent in healthy adult brain tissue but becomes highly expressed by reactive astrocytes at sites of CNS injury. This creates a molecular "homing beacon" that CAQK recognizes and binds to.
Secondary Targets: Proteoglycan Complex
CAQK also interacts with chondroitin sulfate proteoglycans (CSPGs), particularly:
- Versican
- Tenascin-R
- Hyaluronan and proteoglycan link protein 4 (Hapln4)
These lectican family proteoglycans form perineuronal nets in normal brain but are significantly upregulated at injury sites.
Neuroprotective Effects
When bound to injured tissue, CAQK has been shown to:
- Reduce neuroinflammation
- Decrease apoptosis (cell death)
- Limit secondary injury progression
- Improve functional recovery in animal models
Research Applications
CAQK has been studied across multiple CNS injury conditions:
| Application | Studies |
|---|---|
| Spinal Cord Injury (SCI) | 10 of 16 reviewed studies |
| Traumatic Brain Injury (TBI) | 3 of 16 reviewed studies |
| Demyelinating Diseases | 2 of 16 reviewed studies |
| Cartilage Defects | 1 of 16 reviewed studies |
Drug Delivery Platform
Most research has utilized CAQK conjugated to nanoparticles—including liposomal, silicon-based, and extracellular vesicle platforms—to deliver therapeutic agents such as:
- Growth factors
- Anti-inflammatory drugs
- Genetic material
Standalone Therapeutic
Recent research (2025) demonstrated that CAQK alone, without any conjugated drug, improves recovery from acute TBI in mouse and pig models.
Pharmacokinetics
- Administration: Intravenous (IV) infusion
- Distribution: Selectively accumulates in injured brain regions
- Half-life: Short; plasma concentrations return to baseline within 24 hours
- BBB Penetration: Effectively crosses the blood-brain barrier to reach injured tissue
Safety Profile
Preclinical studies consistently report favorable safety:
- No adverse effects observed in heart, liver, spleen, lung, or kidney
- Normal blood chemistry panels
- No apparent toxicity in mouse and pig models
- Preliminary toxicology studies have been encouraging
Current Development Status
CAQK is being developed by Aivocode, a biotech company founded by the researchers who discovered the peptide at Sanford Burnham Prebys Medical Discovery Institute.
Research Milestones
- 2016: Initial discovery and publication in Nature Communications
- 2022: Studies expand to demyelinating diseases
- 2024: Systematic review published summarizing 16 studies
- 2025: Breakthrough neuroprotection study published in EMBO Molecular Medicine
Clinical Path
- Pig studies currently underway with results expected soon
- FDA Phase I clinical trial application planned
- Would be first drug specifically designed to halt TBI brain damage progression
Key Publications
- Mann AP, et al. "A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries." Nature Communications (2016)
- "A neuroprotective tetrapeptide for treatment of acute traumatic brain injury." EMBO Molecular Medicine (2025)
- "Systematic Review of Peptide CAQK: Properties, Applications, and Outcomes." International Journal of Molecular Sciences (2024)
Regulatory Status
- FDA: Not approved; Phase I trial application planned
- WADA: Not currently on prohibited list (as of research cutoff)
- Research Use: Available for research purposes only
CAQK is an investigational compound that has not been approved for human use by any regulatory authority. This information is for educational purposes only.