Sulindac
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Sulindac
- Sulindac: From Musculoskeletal Inflammatory Conditions to Acromesomelic Dysplasia, Hunter-Thompson Type
Sulindac: From Musculoskeletal Inflammatory Conditions to Acromesomelic Dysplasia, Hunter-Thompson Type
One-Sentence Summary
Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) originally used for inflammatory and degenerative joint conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, bursitis and tendinitis. The TxGNN model predicts it may be effective for acromesomelic dysplasia, Hunter-Thompson type, but no clinical trials and no publications currently support this direction, so the prediction rests on the model alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Bursitis, rheumatoid arthritis, ankylosing spondylitis, tendinitis, gout, osteoarthritis (approved indication text is not available in the US license records) |
| Predicted New Indication | Acromesomelic dysplasia, Hunter-Thompson type |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 6 (all cancelled; listed as ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from the data compiled for this report. Based on general knowledge, sulindac is a cyclooxygenase (COX) inhibitor that reduces prostaglandin synthesis, and its efficacy in inflammatory joint disease is established.
The predicted disease is a rare skeletal dysplasia caused by loss-of-function mutations in CDMP1/GDF5, which disrupt BMP/GDF5 signaling during skeletal development. Sulindac’s COX inhibition has no known link to this signaling defect. The very high TxGNN score (0.999) is therefore a model output only, likely reflecting network proximity to other skeletal and joint disease nodes rather than a mechanism-based rationale. At most, NSAIDs might relieve joint pain symptomatically, which is not disease-modifying repurposing.
The other top-ranked predictions show the same pattern. Most are rare congenital skeletal or developmental disorders (brachyolmia, pseudoachondroplasia, brachydactyly-syndactyly syndrome and others) with no supporting evidence. The most biologically coherent candidate is rheumatoid vasculitis (rank 9), an extra-articular complication of rheumatoid arthritis, but NSAIDs are generally not effective for vasculitis, and no evidence was provided for it either.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA072711 | SULINDAC (PuraCap Laboratories / Blu Pharmaceuticals) | Tablet | Not available (cancelled) |
| ANDA072051 | SULINDAC (Sun Pharmaceutical Industries) | Tablet | Not available (cancelled) |
| ANDA072050 | SULINDAC (PD-Rx Pharmaceuticals) | Tablet | Not available (cancelled) |
| ANDA072710 | SULINDAC (PuraCap Laboratories / Blu Pharmaceuticals) | Tablet | Not available (cancelled) |
| ANDA071795 | Sulindac (PD-Rx Pharmaceuticals) | Tablet | Not available (cancelled) |
All six records are cancelled; only the first five are shown. The only dosage form is oral tablet.
Safety Considerations
Contraindications / cautions from the drug-disease knowledge graph (these come from knowledge-graph relationships, not from package insert text):
- Cardiovascular: hypertension, congestive heart failure, myocardial infarction, coronary thrombosis, cardiovascular and heart disease
- Gastrointestinal: peptic ulcer disease (including active peptic ulcer disease), gallbladder disease
- Renal and urinary: kidney disease, nephrolithiasis, acute urate nephropathy
- Hepatic: liver disease
- Haematological: blood coagulation disease, anaemia, hemoglobinopathy
- Autoimmune and connective tissue: systemic lupus erythematosus (including paediatric), connective tissue disease
- Other: bone disease, cartilage disease, substance abuse/dependence
Several of these (bone and cartilage disease, connective tissue disease) overlap with the predicted skeletal indications and should be reviewed carefully.
Drug Interactions (a screening query returned 100 interactions; the main ones from the 20 listed are shown):
- Moderate: acetylsalicylic acid, corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide), mesalazine, balsalazide, metformin, sulfonylureas (chlorpropamide, glimepiride), potassium citrate, potassium bicarbonate, and bowel-preparation agents (picosulfuric acid, polyethylene glycol with electrolytes, sodium sulfate)
- Minor: famotidine, ranitidine, cimetidine, linaclotide
Please refer to the package insert for full safety information, as label warnings were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by the TxGNN model score. There are no clinical trials or publications, no plausible mechanistic link between COX inhibition and the GDF5 signaling defect, and no currently valid US marketing authorization for sulindac.
To proceed, the following is needed:
- Mechanism of action data for sulindac and a credible biological rationale linking it to GDF5/BMP signaling or skeletal development
- Preclinical evidence (for example, cell or animal models of GDF5-related dysplasia)
- Package insert warnings and contraindications to complete safety screening
- Clarification of regulatory and commercial status, since all US licenses are cancelled
- Consideration of whether a more biologically coherent candidate, such as rheumatoid vasculitis, merits a separate evidence review
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.