WhelWomen's Health Evidence Lab
WHEL-C-015 · Exploratory evidence · 3/10

Pentoxifylline for endometriosis

Per Open Targets, pentoxifylline is a Phase 3 clinical candidate for endometriosis acting as an adenosine A2b receptor antagonist.

Origin · ApprovedPathway · Hypothesis-generation · pre-validationEvidence arm · Pathway insightsEvidence silent
How to read thisThe summary above and the proposed mechanism are generated by the model from the sources it ingested, and are written as the model’s reasoning rather than established fact. Any figure quoted from MATRIX is a model-derived association score, not a clinical measurement. How far the published record backs this pair is carried by the score’s own rigor dimension and traced to verbatim sources at the foot of the page.

Hypothesized mechanism

Pentoxifylline may attenuate the inflammatory processes of endometriosis through antagonism of the adenosine A2b receptor.

This is the model’s proposed mechanism from the sources on file, not a demonstrated causal pathway. How well the published record supports it is reflected in the rigor and plausibility dimensions of the score, and traced to the verbatim sources at the foot of the page.

How the score was reached, for this pair

The composite score is the sum of five dimensions, each scored 0 to 2 by the model from the evidence on file. Below is the sub-score this specific pair received on each, with what that dimension measures. It scored 3 of 10 overall, a exploratory reading, from a pathway rated exploratory in strength.

The model’s overall reasoning for this pair is the summary at the top of the page, and the mechanism it proposed is in the section above.

Pathway arm · anchors the headline3.0 / 10 · Exploratory

Scored for women. Female representation not stated — applicability to women uncertain (flagged for full text). (band F4, ×0.75).

Corroboration

Only a single Open Targets database entry is provided, describing one mechanism of action (adenosine A2b receptor antagonism). No independent mechanistic lines converge; there is just one source and one claim.

0 / 2

Rigor

The evidence is a curated database annotation indicating PHASE_3 clinical candidacy for endometriosis, which implies human-relevant context, but no actual study models, data, or outcomes are presented. The claim is a descriptive target/MOA mapping rather than experimental evidence.

1 / 2

Specificity

The claim specifies a defined molecular target (adenosine A2b receptor antagonist), giving moderate specificity of action. However, pentoxifylline is a non-selective phosphodiesterase inhibitor with broad effects, so the single annotated target understates its pharmacology and limits confidence in specificity.

1 / 2

Plausibility

Adenosine A2b receptor signaling has links to inflammation, and endometriosis is an inflammatory condition, providing a plausible target-phenotype connection. However, the claim does not articulate how this target modulates the disease, so the fit is only weakly supported.

1 / 2

Consistency

With only one claim there is no internal conflict, but also no multiple signals to confirm directional agreement. The single annotation is consistent with the proposed use but cannot establish convergence.

1 / 2
How the scoring rubric works, in general

Independent reading, reported beside the score

One outside model cross-reference is reported alongside the composite score. It is recorded separately and is not combined into the score.

MATRIX cross-reference Top 1%

Every Cure’smachine-learned treatment-probability model, drawn from a biomedical knowledge graph. We read its public dataset release, which covers roughly 1,800 drugs and 22,000 diseases. It provides a model-based estimate of how plausible a drug-disease link is given the structure of biomedical knowledge, reported alongside the substrate’s own evidence.

For this pair. MATRIX places this pair at Top 1%, with a treat-score of 3.65 (higher is better; across the pairs we cover, scores span about 3.1 to 4.5).

Scored over MATRIX’s own entities, confirming the same drug and disease: CHEBI:7986 (drug) and MONDO:0005133 (disease). Validate against the source: Every Cure’s MATRIX dataset ↗.

More on the MATRIX cross-reference and its provenance

Regulatory & development status

Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for endometriosis (on-label) or approved for something else (off-label), whether the molecule is available as a generic or a single-source brand still under patent, and how far it has been studied as a therapy for this condition. Each fact is drawn from a public US source and reported beside the score; none of it is folded into the score.

This is descriptive context, not regulatory advice. It maps the landscape a 505(b)(2)route would build on (an already-approved active ingredient proposed for a new indication), but it is not a 505(b)(2) viability assessment, and says nothing about whether any particular development path is advisable. “Approved” means FDA-approved (US); approvals elsewhere are out of scope.

Approval relationship Off-label

Read from the drug’s FDA label via DailyMed, the US National Library of Medicine’s label repository. A label is only counted when it carries an FDA-approved marketing category (an NDA, ANDA, or biologic BLA); dietary supplements, homeopathics, and OTC-monograph products are not FDA-approved drugs and are excluded.

For this pair. The drug has an FDA-approved label, but for a different indication, so using it for this condition would be off-label.

Generic & patent supply Generic available

Read from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), using single-ingredient products only so that patents on novel branded combination formulations are never attributed to the base molecule.

For this molecule. A live ANDA lists this active ingredient, so the basic molecule is available as a generic (off-patent in its basic form).

PENTOXIFYLLINE · ANDA (generic) · 400MG · rx · approved Jul 9, 1997
PENTOXIFYLLINE · ANDA (generic) · 400MG · discn · approved Sep 4, 1998
PENTOXIFYLLINE · ANDA (generic) · 400MG · discn · approved Sep 3, 1999
PENTOXIFYLLINE · ANDA (generic) · 400MG · rx · approved Jun 9, 1999
PENTOXIFYLLINE · ANDA (generic) · 400MG · discn · approved Jul 20, 1998

Clinical-trial stage, for this condition Phase 3

Read from ClinicalTrials.gov (US National Library of Medicine). A trial only counts when the drug appears as an experimental or active-comparator intervention in an interventional study of this condition; mechanistic, drug-interaction, post-marketing (Phase 4), and comparator-background uses are excluded, so this reflects the drug being tested as a therapy for endometriosis.

For this pair. Studied in 1 qualifying interventional trial · highest stage reached Phase 3 · completed.

NCT00632697 · Phase 3 · completed
The regulatory and trial sources this status is drawn from

Layers not covered for this pair

Sex-specific pharmacokineticsNone on file

Not covered for this pair. This layer holds documented sex-specific pharmacokinetics for a limited set of drugs, and this compound is not among them yet. A blank here means the drug is not covered by the layer, not that no sex difference exists.

More on the sex-specific pharmacokinetics layer and its sources
Cycle-phase dependenceNone on file

Not covered for this pair. The cycle-phase layer is seeded for the strongest-evidence cases so far (PMDD), and this pair is not among them yet. A blank here means the pair is not covered by the layer, not that the effect was found to be phase-independent.

More on the cycle-phase layer and its sources

Source evidence · what the pipeline ingested

These are the sources the pipeline ingested to detect and score this signal, the published literature the model actually read, each tagged by study type. Where the model combined findings the claim is marked as a synthesis (S), and where the literature disagrees the contradiction is shown (!).

Every source below belongs to this signal’s evidence arm, Pathway insights. Whel reads each drug-condition pair through four such arms, each held to its own inclusion bar; a signal is surfaced through one of them.

  • 1Per Open Targets (retrieved 2026-06-16), PENTOXIFYLLINE (a Small molecule) is a clinical candidate for endometriosis (maximum clinical stage PHASE_3); its mechanism of action is Adenosine A2 receptor antagonist on target adenosine A2b receptor. Open Targets · mechanistic

These are the verbatim sources the pipeline surfaced and read; they may not be the full published record for a pair, and the score reflects the strength and agreement of the evidence rather than its volume. The strength of these source types is what the rigor dimension of the score reads off. MATRIX, sex-specific pharmacokinetics, and cycle phase are separate layers the pipeline does not ingest, external cross-references reported beside the score, and they link to their own sources in their sections above.

The primary sources and pipelines this evidence is drawn from