Description
Survodutide – Advanced Biochemical Mechanism Profile
(Dual GLP-1 / Glucagon Receptor Agonist; Peptide Research Compound)
Survodutide is a synthetic peptide designed to act as a co-agonist at both the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R).
Both receptors are class B GPCRs primarily coupled to Gs, producing adenylyl cyclase activation → cAMP accumulation → PKA signaling, alongside secondary ERK1/2 and PI3K-Akt cascades.
✅ 1. Primary Molecular Targets
A. GLP-1 Receptor (GLP-1R) – Gs-coupled GPCR
Ligand binding causes:
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Gsα activation → adenylyl cyclase
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↑ cAMP
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PKA activation
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CREB phosphorylation
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Gene transcription changes in metabolic tissues
B. Glucagon Receptor (GCGR) – Gs-dominant GPCR
Activation leads to:
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Adenylyl cyclase → cAMP ↑
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Regulation of glycogen metabolism enzymes
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Secondary contributions from Gq/PLC/IP₃ in select cell systems
✅ 2. Intracellular Signaling Pathways
A. cAMP / PKA / CREB (Primary Pathway)
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cAMP accumulation activates PKA
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PKA phosphorylates CREB
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CREB binds cAMP-response elements (CREs) on metabolic and mitochondrial genes
Representative CREB-responsive targets:
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PPARGC1A (PGC-1α)
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NRF1, TFAM (mitochondrial biogenesis)
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SLC2A4 (GLUT4)
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PDK4
B. PI3K → Akt Pathway
Triggered downstream of GLP-1R signaling:
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PI3K activation → Akt phosphorylation
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Influences transcription of metabolic and stress-response genes
Measured targets in research systems:
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FOXO1, GSK-3β, SREBP-1c
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BCL2, MCL1 (mitochondrial survival signaling)
C. MAPK / ERK1/2
Both GCGR and GLP-1R can signal through:
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Ras → Raf → MEK → ERK1/2
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ERK nuclear translocation → immediate-early gene expression
ERK-responsive genes:
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FOS, JUN, EGR1
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CCND1 (cell-cycle progression)
✅ 3. Second Messenger Systems
| Component | Role in Survodutide Signaling |
|---|---|
| cAMP ↑ | Central second messenger for both receptors |
| PKA | Phosphorylates CREB, ion channels, metabolic enzymes |
| CREB | Drives transcription of mitochondrial and metabolic genes |
| ERK1/2 | Mitogenic and transcriptional responses |
| Ca²⁺ | Can be elevated via GCGR-linked PLC/IP₃ pathways |
✅ 4. Enzymatic Targets and Metabolic Regulators
Survodutide signaling influences expression/activity of:
Glycogen metabolism enzymes
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Glycogen synthase (GYS)
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Glycogen phosphorylase (PYGL/PYGM)
Mitochondrial regulators
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CPT1, ACADL, PGC-1α
Lipid & carbohydrate transport
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SLC2A4 (GLUT4)
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CD36
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FABP family
✅ 5. Gene Targets Commonly Monitored in Research
| Category | Example Genes |
|---|---|
| cAMP/CREB Axis | CREB1, NR4A1, PPARGC1A (PGC-1α) |
| Mitochondrial Biogenesis | NRF1, TFAM, COX genes |
| Glucose & Lipid Metabolism | SLC2A4 (GLUT4), CPT1B, ACADL, PDK4 |
| MAPK-Responsive | FOS, JUN, EGR1, CCND1 |
| Cell Survival / Stress | BCL2, MCL1, SOD2 |
✅ Mechanistic Summary
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Dual GLP-1R and GCGR agonist
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Activates Gs → adenylyl cyclase → cAMP → PKA → CREB
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Secondary activation of ERK1/2 and PI3K/Akt
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Drives transcription of metabolic, mitochondrial, and immediate-early genes in model systems
Research-Only Classification
Survodutide is supplied exclusively for in-vitro laboratory research.
Not approved for human or animal administration, therapeutic use, or any biological application outside controlled research environments.