Proguanil
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Proguanil: From Malaria to Smouldering Systemic Mastocytosis
One-Sentence Summary
Proguanil is an antimalarial, originally used to treat and prevent Plasmodium falciparum malaria. The TxGNN model predicts it may be effective for Smouldering systemic mastocytosis, but there are currently 0 clinical trials and 0 publications supporting this prediction, so it is a model-based hypothesis only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Plasmodium falciparum malaria / malaria |
| Predicted New Indication | Smouldering systemic mastocytosis |
| TxGNN Prediction Score | 92.12% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, proguanil is a prodrug whose metabolite, cycloguanil, inhibits dihydrofolate reductase in the malaria parasite. Proguanil itself has also been reported to have mitochondrial effects. Its efficacy in malaria is established.
However, neither of these mechanisms has a documented connection to KIT-driven mast cell proliferation, which underlies mastocytosis. The data compiled for this report show no mechanistic link between proguanil and this disease.
The high score (0.92) is a knowledge-graph prediction only. The other top predictions include related mastocytosis conditions (lymphoadenopathic mastocytosis with eosinophilia, 0.90; systemic mastocytosis, 0.86). They likely share the same graph-derived signal rather than reflecting biology. The remaining predictions are mainly renal and ciliopathy-related disorders (such as polycystic kidney disease and Joubert syndrome with renal defect), and none has trial or literature support.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09761P | MALARONE TABLET | Tablet, film coated | Not stated in the data compiled for this report |
Proguanil is registered in Singapore under one single-ingredient licence, valid, for oral use.
Safety Considerations
- Contraindications (from knowledge-graph associations, not label text): liver failure, liver disease, gallbladder disease, hyperglycemia, chronic diarrheal disease.
- Drug Interactions: 33 interactions were identified; the 20 listed in the data are summarised below.
- Major (2): auranofin, aurothioglucose.
- Moderate (17):
- Antacids and adsorbents: aluminum hydroxide, calcium carbonate, kaolin, magaldrate, magnesium hydroxide, sodium bicarbonate.
- Anticoagulants: warfarin, dicoumarol, anisindione.
- Others: sapropterin, glucarpidase, iodide I-131, iodide I-123, fenofibrate, apalutamide, armodafinil, artemether.
- Minor (1): brivaracetam.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a knowledge-graph score. There are no clinical trials, no literature, and no supported mechanistic link between proguanil and mast cell disease. The evidence level is L5.
To proceed, the following is needed:
- Mechanism of action data for proguanil and its metabolite, and an assessment of any plausible link to mast cell biology (such as KIT signalling)
- Preclinical or literature evidence for mastocytosis
- The Singapore package insert, for warnings, contraindications and the approved indication
- A route and formulation compatibility assessment for the new indication
- A safety review covering the hepatic and gallbladder associations and the interactions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.