Description
Cagrilintide – Technical Biochemical Mechanism Profile
(Long-Acting Amylin Receptor Agonist; Class-B GPCR Modulator – Research Use Only)
Cagrilintide is a synthetic amylin-mimetic peptide with enhanced pharmacokinetic stability and selective affinity for amylin receptor subtypes formed by calcitonin receptors (CTR) in heterodimeric association with RAMP1/2/3 (Receptor Activity-Modifying Proteins).
In vitro research demonstrates activation of cAMP-PKA, CREB-dependent transcription, and neuronal and gastrointestinal signaling pathways involved in metabolic regulation.
✅ 1. Primary Molecular Targets
Cagrilintide binds and activates amylin receptors:
| Receptor Form | Structure | Expression |
|---|---|---|
| AMY1 | CTR + RAMP1 | CNS & enteric neurons |
| AMY2 | CTR + RAMP2 | Hypothalamus, brainstem |
| AMY3 | CTR + RAMP3 | Vagal/enteric circuits |
All are Gs-coupled Class-B GPCRs → activation of adenylate cyclase → cAMP↑.
✅ 2. Core Signal Transduction
AMY1–3 Receptor Activation →
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Gs protein coupling
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Adenylate cyclase activation
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↑ cAMP
-
PKA phosphorylation of CREB
-
CRE-controlled transcriptional programs
Secondary pathways
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ERK1/2 phosphorylation (MAPK axis)
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Ca²⁺-dependent vesicle signaling via neuronal circuits
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Modulation of NO/VIP/cholinergic enteric pathways
✅ 3. Enzymes & Second Messengers
| Component | Function in Cagrilintide Signaling |
|---|---|
| Adenylate Cyclase (ADCY) | Converts ATP → cAMP |
| PKA (Protein Kinase A) | Phosphorylates CREB, ion channels, GPCR regulators |
| CREB (pCREB) | Transcription of satiety/metabolic genes |
| ERK1/2 | Synaptic, neuroendocrine transcription output |
| Ca²⁺ | Neurotransmitter release from CNS/enteric neurons |
| NO Synthase (NOS1) | Vagal/enteric modulation of gastric motility |
✅ 4. Gene-Level Targets Monitored in Research
| Functional Category | Example Genes |
|---|---|
| Satiety / Neuropeptide signaling | ↑ POMC, CART, ↓ NPY, AgRP |
| cAMP-PKA–CREB machinery | ADCY1, PRKACA, CREB1 |
| Enteric neuromodulation | NOS1, VIP, CHAT, CHRM1/3 |
| Glucose regulation (β-cell assays) | INS, PDX1, MAFA, SLC2A2 (GLUT2) |
| GPCR metabolic network | CALCR, RAMP1/2/3, GLP1R, GCGR, GIPR |
✅ 5. CNS / Hypothalamic Pathways
In metabolic-neuron research models:
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POMC/CART neurons activated → anorexigenic transcription
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NPY/AgRP neurons suppressed
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CREB binding to POMC promoter increases transcriptional output
Key transcription factor:
-
pCREB (Ser133-phosphorylated)
✅ 6. Gastrointestinal & Vagal Signaling
Amylin-receptor activation alters enteric-nerve signaling:
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↑ NO via NOS1
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↑ VIP release
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↓ cholinergic smooth-muscle activation
These pathways are monitored through:
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nNOS (NOS1) expression, VIP, CHRNA7, CHRM1/3
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Reduced gastric motility and altered intestinal transit in neural cell models
✅ 7. Pathway Summary
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Receptor Type: Class-B GPCR (AMY1–3 complexes)
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Primary Cascade: Gs → Adenylate Cyclase → cAMP ↑ → PKA → pCREB
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Secondary Cascades: ERK1/2, Ca²⁺-dependent neurotransmission, NO/VIP signaling
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Main Gene Markers: POMC, CART, ADCY1, PRKACA, CREB1, NOS1, VIP
✅ Mechanistic Summary
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Synthetic long-acting amylin receptor agonist
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Activates AMY1–3 GPCRs → cAMP/PKA/pCREB signaling
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Modulates hypothalamic neuropeptide transcription (↑ POMC/CART, ↓ NPY/AgRP)
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Influences enteric NO/VIP pathways and neuroendocrine secretion
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Gene-level changes observed in metabolic and neuronal cell models
✅ Research-Only Classification
Cagrilintide is provided exclusively for in-vitro laboratory research.
Not approved for human or animal use, injection, ingestion, or biological application.