Compound Evidence Catalog¶
Scope¶
This catalog records compounds and exposures with reported activity on NLRP3, urate handling, or related pathways. It is an evidence-routing and experiment-design surface, not a recommended stack, prescribing guide, dosing schedule, or access guide.
Approved drugs appear only as research comparators. Evidence from another indication does not establish gout efficacy. Dietary availability, supplement availability, or a familiar production route does not establish adequate exposure, safety, target engagement, or benefit.
Species-gap rule: prefer human-cell potency when available and apply the cross-species standard in
chembl-cross-check.mdbefore translating rodent results.
Candidate evidence summary¶
The table records the highest relevant evidence class represented in the current dossier and the key unresolved translation question. Exact study design, material, concentration, and endpoint must be rechecked in the linked evidence home before an experiment uses the claim.
| Candidate | Evidence level | Reported gout-relevant mechanism | Current boundary | Evidence home |
|---|---|---|---|---|
| BHB / ketone bodies | In Vitro + Animal Model | NLRP3 priming, potassium-efflux, and ASC-related effects | Human gout exposure and simultaneous renal-urate effects remain unresolved | BHB / ketones |
| Fasting | Mechanistic Extrapolation | Autophagy, AMPK/mTOR, endogenous ketone production | Not a validated NLRP3 or acute-flare intervention | NLRP3 exploit map |
| KPV | In Vitro | PepT1-related uptake and an NF-κB reporter effect in named intestinal/Jurkat systems | Direct MSU activity, synovial exposure, and a gout route are unestablished | KPV |
| BPC-157 | Animal Model + Mechanistic Extrapolation | Cytoprotection and nitric-oxide-related signaling | Adjacent-model evidence does not establish gout efficacy | BPC-157 |
| Sulforaphane | In Vitro + Animal Model | Nrf2/NF-κB and NLRP3-related effects in MSU models | Human gout exposure-response is unknown | NLRP3 exploit map |
| Theaflavins | In Vitro + Animal Model | NLRP3–NEK7, inflammasome, and renal-transporter effects | Human gout efficacy and free exposure are unknown | Theaflavins |
| Houttuynia cordata polysaccharides | In Vitro + Animal Model | Complement and context-dependent inflammatory effects | Exact material, likely intestinal delivery, and direct MSU effects remain unresolved | Houttuynia |
| Oridonin | In Vitro + Animal Model | Covalent NLRP3 inhibition and inflammasome suppression | Human gout exposure, selectivity, and safety remain open | Oridonin |
| Exact RvD1 and MaR1 | Animal Model + In Vitro | Distinct MSU-model neuroimmune and Prdx5/AMPK/Nrf2-associated effects | Human gout exposure and efficacy are unestablished; EPA/DHA precursors are a separate conversion experiment | SPM pathway |
| Tart-cherry preparations | Clinical Trial, preparation-specific | Candidate xanthine-oxidase and inflammatory effects | Preparation, exposure, and endpoint heterogeneity prevent a class-wide conclusion | Gout deep dive |
| NAC / glutathione-axis perturbation | In Vitro + Animal Model | Redox and mitochondrial-ROS modulation upstream of NLRP3 | Gout-relevant compartmental exposure and efficacy are unestablished | NLRP3 exploit map |
| EGCG | In Vitro + Animal Model | NF-κB, proteasome, caspase-1, and IL-1-related effects | Food and concentrated-extract exposures are not interchangeable; human gout efficacy is unknown | EGCG |
| Limonene | Animal Model | Nrf2 and TLR4-related effects in an MSU model | Human translation and exposure adequacy are unknown | Cannabinoids / terpenes |
| Lactoferrin | In Vitro + Animal Model in adjacent systems | Material-specific iron, inflammatory, barrier, or mitophagy/pyroptosis hypotheses | No direct MSU-gout multi-chokepoint effect is established; exact material and compartment must be tested separately | Lactoferrin |
| Carnosine | Animal Model | Urate and NLRP3-related effects in hyperuricemia models | Human gout exposure and serum-carnosinase effects remain open | Carnosine |
| Eurycoma longifolia / Tongkat Ali | Clinical Trial, endpoint-specific | Reported hormone and urate-related effects | Product identity, mechanism, and reproducibility must remain source-specific | Androgen natural modulation |
| Quercetin | In Vitro + Animal Model | 5-LOX/LTB4, NF-κB, XO, and mixed ABCG2 effects | Direct human gout efficacy and intestinal urate-flux effects are unmeasured | ABCG2 modulators |
| Beta-caryophyllene | Animal Model | CB2/TLR4/NLRP3-related effects in MSU models | Human gout translation and exposure remain unknown | Cannabinoids / terpenes |
| Vitamin D / VDR signaling | Mechanistic Extrapolation for gout | VDR and NF-κB-related signaling | A mechanistic link does not define a gout-specific target exposure | NLRP3 exploit map |
| Disulfiram | In Vitro + Clinical Trial in another indication | GSDMD pore blockade | Approved use does not establish a gout indication, regimen, or safety profile | Disulfiram |
| Tranilast | In Vitro + Animal Model; Clinical exposure in other indications | NACHT-domain NLRP3 inhibition | Human gout efficacy is unestablished | NLRP3 exploit map |
| Fermented-food metabolites | Mechanistic Extrapolation, material-specific | Candidate autophagy, SPM, and microbiome-metabolite effects | Presence in food does not establish delivered exposure or target engagement | NLRP3 exploit map |
| Engineered luminal UOX, chassis unresolved | Mechanistic Extrapolation | Candidate local urate degradation | Physiological flux, systemic effect, dose, safety, containment, and chassis remain unresolved | Gut-lumen sink |
Interaction hypotheses¶
ABCG2 and luminal UOX¶
Intestinal ABCG2 is one contributor to luminal urate supply, so its function is a study variable for the engineered-UOX hypothesis. Pharmacology assays identify several catalog compounds as substrates, inhibitors, or expression modulators, but those data do not establish an interaction with urate flux at the relevant exposure.
| Compound | Reported ABCG2 effect | Evidence | Experimental implication |
|---|---|---|---|
| Curcumin | Functional BCRP/ABCG2 inhibition in vitro; selective intestinal BCRP inhibition reported in cynomolgus monkeys | In Vitro + Animal Model; tested substrates were not urate | Candidate inhibitor control; measure intestinal urate flux directly |
| Quercetin | Substrate/inhibitor in pharmacology assays; transcriptional upregulation reported after repeated animal exposure | In Vitro + Animal Model, context-dependent | Separate acute function from expression and chronicity |
| EGCG | Reduced mitoxantrone-assayed BCRP activity after exposure in MCF-7Tam cells; Yu's mouse phenotype reports renal Oat1/Oct1 and Urat1/Glut9, not ABCG2 in the primary abstract | In Vitro + Animal Model, different systems and endpoints | Measure free parent/metabolites, ABCG2 protein and attribution, and intestinal urate flux together |
| Genistein / soy isoflavones | BCRP substrate/inhibitor signals | In Vitro | Food and concentrated-material exposures require separate controls |
ABCG2 genotype, hormone state, exposure, intestinal segment, and chronicity are experimental strata. They do not identify a personalized combination or timing rule. Candidate inducer arms such as sulforaphane, fermentable-fiber-derived butyrate, and AhR-active indoles also require direct urate-flux testing.
Mechanistic overlap¶
The following clusters define factorial experiments, not combinations to use:
| Cluster | Candidates | Question |
|---|---|---|
| Nrf2-related signaling | Sulforaphane, quercetin, oridonin, limonene, and exact MaR1 | Are effects redundant, additive, or context-dependent at matched target engagement? |
| NF-κB priming | Sulforaphane, EGCG, quercetin, carnosine, curcumin; KPV as a separate uptake/priming conjecture | Which exact materials reproduce under matched MSU exposure, and do any effects remain after mechanism attribution? |
| XO-related activity | Tart-cherry preparations, quercetin, EGCG | Does the combination exceed either arm after exposure is matched? |
| CP2 / NLRP3 assembly | Oridonin, beta-caryophyllene, tranilast, dapansutrile, BHB | Which molecular readout moves, and does node diversity translate to nonredundancy? |
| Resolution / cytoprotection | Exact RvD1 and MaR1; BPC-157 as a separate adjacent repair lead | Does an exact material change resolution or later repair independently of acute inflammasome suppression? |
| Autophagy | Fasting-state biology, spermidine, trehalose, rapamycin | Is autophagy target engagement causal for the gout-relevant endpoint? |
No cluster is presumed additive. Test each arm against the same comparator before testing a prespecified interaction.
Safety interaction signals¶
These are study-design and exclusion-review signals, not instructions for starting, stopping, holding, monitoring, or combining a compound.
| Signal | Candidate combination or context | Research consequence |
|---|---|---|
| Hepatic stress | EGCG, disulfiram, concentrated curcumin, alcohol, acetaminophen | Require compound-specific hepatic evidence and prespecified safety exclusions before combination testing |
| Bleeding / platelet effects | Omega-3, EGCG, quercetin, anticoagulants, antiplatelets | Treat concomitant therapy as a safety exclusion or stratification variable under clinical oversight |
| CYP3A4 interaction | Quercetin, EGCG, oridonin, limonene with CYP3A4 substrates | Confirm clinically relevant free exposure; in-vitro inhibition alone is insufficient |
| Disulfiram–ethanol reaction | Disulfiram with any ethanol-containing exposure | Exclude uncontrolled ethanol exposure from a disulfiram study design |
| Vitamin K / anticoagulation | Vitamin K2 or natto with warfarin | Treat as a known interaction context requiring clinical protocol ownership |
| Calcium handling | Vitamin D exposure with thiazide therapy | Prespecify calcium-related eligibility and safety endpoints in any relevant study |
Conditional engineered luminal UOX¶
Engineered luminal UOX is not a supplement, available product, home-fermentation format, or dosing recommendation. Yeast, koji, and live biotherapeutic hosts are candidate configurations, not validated delivery routes. Parent-organism food or manufacturing history does not establish the safety, containment, activity, exposure, or efficacy of an engineered strain.
Required sequence:
- Build and characterize exact configurations.
- Establish a physiologically relevant reaction regime in validation §1.33.
- Test antioxidant loss and peroxide safety in §1.36.
- Measure functional urate disposal and only then test systemic outcomes.
- Compare chassis only under matched expression, localization, stability, containment, and safety conditions.
Experimental sequencing¶
- Start from a stated gout weakness and a source-verified mechanistic prediction.
- Verify exact material identity and relevant exposure.
- Test a single candidate against a gout-relevant comparator before a combination.
- Separate urate handling, inflammasome activity, resolution, and clinical outcomes.
- Prespecify interaction risks, stopping rules, and a nonredundancy criterion.
- Treat null, inverted, or exposure-limited results as reasons to revise or stop the hypothesis.
Research catalog only. It does not define clinical care.