ID: h-ecfaa2cbb2
Hypothesis
Parthenolide perturbs adenosine transport or metabolism upstream of ADORA2A
Covalent modulation of transporters or metabolic enzymes changes local receptor occupancy in a context-dependent manner.
EvidencePending (0%)📖 1 cit🗣 1 debates✓ 5 support✗ 1 oppose
✓ All Quality Gates Passed
🧪 Overview
Covalent modulation of transporters or metabolic enzymes changes local receptor occupancy in a context-dependent manner.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["Adenosine Accumulation<br/>Metabolic Stress or Hypoxia"]
B["ADORA2A Engagement<br/>Gi-coupled Anti-inflammatory Receptor"]
C["cAMP Suppression<br/>PKA Activity Reduction"]
D["Microglial Activation Threshold Raised<br/>Pro-inflammatory Mediator Release Reduced"]
E["Neuroprotection<br/>Reduced Glutamate Toxicity and Oxidative Stress"]
F["ADORA2A Blockade<br/>Pro-inflammatory Activation Restored"]
A --> B
B --> C
C --> D
D --> E
F -.->|"counteracts"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix5 supports1 contradicts
Supports
Parthenolide inhibits neuroinflammation via adenosine and A2A receptor signaling.
Supports
Parthenolide ameliorates neurological deficits and neuroinflammation in mice with traumatic brain injury by suppressing STAT3/NF-κB and inflammasome activation.
Supports
Parthenolide, an NF-κB Inhibitor Ameliorates Diabetes-Induced Behavioural Deficit, Neurotransmitter Imbalance and Neuroinflammation in Type 2 Diabetes Rat Model.
Supports
Arglabin regulates microglia polarization to relieve neuroinflammation in Alzheimer's disease.
Supports
Parthenolide attenuates LPS-induced fever, circulating cytokines and markers of brain inflammation in rats.
Contradicts
Parthenolide promiscuity may make the apparent specificity illusory.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — ADORA2A
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for ADORA2A from GTEx v10.
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ADORA2A.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
💰 Estimated Development
Cost
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Timeline
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▲ 0.0%
Volatility
Medium
0.0214
Events (7d)
1
Price History
▼4.4%💾 Resource Usage
LLM Tokens
1,598
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Total Cost
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🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF human SH-SY5Y neuroblastoma cells are treated with parthenolide (10 μM, 2-hour incubation), THEN extracellular adenosine concentration will increase by >50% compared to vehicle-treated controls, as | Extracellular adenosine will increase from baseline ~200 nM to >300 nM in parthenolide-treated cultures | — no observation — | pending | 0.65 |
| IF rat primary cortical neurons are pretreated with NBTI (10 μM, equilibrated nucleoside transporter inhibitor) followed by parthenolide (10 μM, 2 hours), THEN the parthenolide-induced increase in ext | Adenosine concentration in parthenolide+NBTI condition will not differ significantly from NBTI-only control (within 20% of baseline) | — no observation — | pending | 0.55 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF human SH-SY5Y neuroblastoma cells are treated with parthenolide (10 μM, 2-hour incubation), THEN extracellular adenosine concentration will increase by >50% compared to vehicle-treated controls, as measured by HPLC-MS quantification of cell culture supernatant.
Predicted outcome: Extracellular adenosine will increase from baseline ~200 nM to >300 nM in parthenolide-treated cultures
Falsification: Extracellular adenosine remains within 20% of vehicle control levels (<240 nM) despite parthenolide treatment
pendingconf 55%
IF rat primary cortical neurons are pretreated with NBTI (10 μM, equilibrated nucleoside transporter inhibitor) followed by parthenolide (10 μM, 2 hours), THEN the parthenolide-induced increase in extracellular adenosine will be abolished (>80% attenuation) compared to parthenolide alone, as measure
Predicted outcome: Adenosine concentration in parthenolide+NBTI condition will not differ significantly from NBTI-only control (within 20% of baseline)
Falsification: Parthenolide+NBTI condition shows adenosine levels comparable to parthenolide alone, indicating the effect is independent of equilibrative nucleoside transporters
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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