RALOXIFENE for menopause
Per an Open Targets annotation, RALOXIFENE is a Phase 2 clinical candidate for menopause acting as an estrogen receptor beta modulator on estrogen receptor 2 (ESR2).
Hypothesized mechanism
RALOXIFENE modulates estrogen receptor beta (ESR2) signaling, potentially substituting for declining estrogen activity in menopause-related tissues.
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 4.5 of 10 overall, a emerging reading, from a pathway rated emerging 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.
Scored for women. Female representation not stated — applicability to women uncertain (flagged for full text). (band F4, ×0.75).
Corroboration
Only a single line of evidence is present: one Open Targets database entry linking RALOXIFENE to estrogen receptor 2 (ESR2). No independent mechanistic lines converge to support the claim.
Rigor
The evidence is a curated database annotation (Open Targets) citing a Phase 2 clinical stage for menopause, which implies human-relevant context but provides no actual study data or model details. It is essentially a target-tractability annotation rather than experimental rigor.
Specificity
The claim specifies a defined molecular action: RALOXIFENE acts as an estrogen receptor beta modulator on the named target estrogen receptor 2 (ESR2). This is a specific drug-target interaction as stated.
Plausibility
Modulation of estrogen receptor beta (ESR2) is a highly plausible mechanism for a menopause-related phenotype given estrogen signaling's central role in menopausal physiology. The target-phenotype fit is strong as a SERM acting on an estrogen receptor.
Consistency
There is only one signal (a single database annotation), so there is no internal disagreement, but also no multiple signals to confirm directional consistency. Consistency cannot be meaningfully demonstrated with a single source.
Layers not covered for this pair
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 →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), RALOXIFENE (a Small molecule) is a clinical candidate for menopause (maximum clinical stage PHASE_2); its mechanism of action is Estrogen receptor beta modulator on target estrogen receptor 2. 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 →