Maraviroc
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Maraviroc: From HIV-1 Infection (CCR5 Antagonist) to Multiple Endocrine Neoplasia
Note: This evidence pack does not contain a confirmed original-indication text or MOA record (see Data Gap DG002). The “HIV-1 infection / CCR5 antagonist” framing above is inferred from the repurposing-rationale text and the surrounding literature context in this pack (e.g. papers on “antiretroviral therapy,” “HIV disease,” “HIV+ patients ART treated”), not from a verified regulatory source.
One-Sentence Summary
Maraviroc is a CCR5 antagonist most commonly associated with HIV-1 antiretroviral therapy, though no confirmed original-indication or mechanism-of-action record exists in this evidence pack. TxGNN’s top prediction is multiple endocrine neoplasia (MEN), but this candidate has zero supporting clinical trials and zero literature, and the model’s own rationale states no known mechanistic link between CCR5 and MEN pathogenesis (RET/MEN1 mutations) exists.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in evidence pack (contextually CCR5 antagonist / HIV-1 therapy — unconfirmed, see DG002) |
| Predicted New Indication | Multiple Endocrine Neoplasia |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L5 |
| US Market Status | ✗ Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in this evidence pack (Data Gap DG002, High severity). Based on the repurposing-rationale text attached to this and other candidates in the same evidence pack, maraviroc is consistently identified as a CCR5 antagonist.
The evidence pack’s own analysis states explicitly that there is no known intersection between the CCR5 antagonist mechanism and the RET/MEN1 gene-mutation pathways that drive multiple endocrine neoplasia. No preclinical, epidemiological, or clinical data connecting CCR5 signaling to MEN pathogenesis were found.
As a result, this candidate rests entirely on the TxGNN model’s statistical prediction score, with no mechanistic, preclinical, or clinical corroboration. This is the weakest tier of evidence in the scoring framework (L5).
Clinical Trial Evidence
Currently no related clinical trials registered
Literature Evidence
Currently no related literature available
Safety Considerations
Please refer to the package insert for safety information.
Note: Both TFDA label warnings/contraindications (DG001, Blocking severity) and drug-drug interaction data (query returned “not_found”) are unavailable, which by itself blocks progression to a formal safety evaluation (S1) for this drug.
Other Candidates in This Evidence Pack
Ten indications were screened for maraviroc; only the top-ranked one is detailed above per report scope. For context, the full ranked set (evidence quality varies substantially — several lower-ranked candidates have stronger mechanistic grounding than the top prediction):
| Rank | Predicted Indication | TxGNN Score | Evidence Level | Recommendation | Note |
|---|---|---|---|---|---|
| 1 | Multiple endocrine neoplasia | 99.82% | L5 | Hold | No known CCR5–MEN mechanistic link |
| 2 | Acne (disease) | 99.76% | L5 | Hold | No known CCR5–acne link |
| 3 | Primary cutaneous T-cell lymphoma | 99.72% | L4 | Hold | CTCL mainly involves CCR4, not CCR5; literature only tangential |
| 4 | Pediatric SLE | 99.71% | L5 | Hold | CCR5Δ32/SLE link exists in general literature, but none cited here |
| 5 | Primary cutaneous T-cell non-Hodgkin lymphoma | 99.50% | L4 | Hold | Duplicate of rank 3, same tangential citation |
| 6 | Primary cutaneous B-cell lymphoma | 99.38% | L5 | Hold | No known mechanistic link |
| 7 | Candidiasis | 99.28% | L4 | Hold | Cited literature describes candidiasis as an ART side effect, not a maraviroc treatment effect |
| 8 | Complement component 4a deficiency | 99.24% | L5 | Hold | No known mechanistic link |
| 9 | Cytomegalovirus infection | 99.23% | L4 | Research Question | CCR5’s role in immune trafficking plausible in HIV/CMV co-infection, but evidence is indirect |
| 10 | HER2-positive breast carcinoma | 99.22% | L4 | Research Question | Strongest direct molecular rationale: CCL5 (CCR5’s endogenous ligand) drives trastuzumab resistance via ERK — theoretically blockable by a CCR5 antagonist |
Rank 10 (HER2-positive breast carcinoma) and rank 9 (CMV infection) carry the only “Research Question” recommendations in the set and may warrant separate evaluation if this pipeline is to be pursued further.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked candidate (multiple endocrine neoplasia) has no supporting clinical, literature, or mechanistic evidence beyond the raw TxGNN score, and the model’s own rationale rules out a plausible biological connection. Combined with a Blocking-severity gap in TFDA safety data and an unmarketed status in the reference market, there is no basis to advance this specific candidate.
To proceed, the following is needed:
- TFDA/regulatory label data (warnings, contraindications) — currently a Blocking data gap (DG001)
- Confirmed mechanism-of-action and original-indication record for maraviroc (DG002)
- If pursuing repurposing further, redirect evaluation toward the higher-mechanistic-plausibility candidates identified in this pack (HER2-positive breast carcinoma, CMV infection) rather than the top TxGNN-ranked but mechanistically unsupported MEN prediction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.