Component

4-Hydroxytamoxifen

4-Hydroxytamoxifen. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

  1. BR-DIM reduced plasma 4-hydroxytamoxifen compared with placebo.

    3,3'-Diindolylmethane / DIM → Plasma 4-hydroxytamoxifen concentration source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/28560655.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28", "start_char": 0, "end_char": 1823, "text_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28"}
    experimental_model
    Randomized double-blind placebo-controlled trial
    exposure
    BR-DIM 150 mg twice daily for 12 months
    limitations
    Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    130 women prescribed tamoxifen; 98 completed
    plain_language
    A second active metabolite also fell.
    primary_references
    [dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7
    tissue_or_cell_type
    Estrogen biomarkers and tamoxifen metabolites

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1065–1076

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft

    ### dim-4oh-tam-lower BR-DIM reduced plasma 4-hydroxytamoxifen compared with placebo. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second active metabolite also fell. organism: 130 women prescribed tamoxifen; 98 completed tissue_or_cell_type: Estrogen biomarkers and tamoxifen metabolites experimental_model: Randomized double-blind placebo-controlled trial limitations: Biomarker and pharmacokinetic endpoints, not recurrence or survival. The causal enzyme mechanism and effect on tamoxifen clinical benefit were not determined. exposure: BR-DIM 150 mg twice daily for 12 months evidence_span: {"source_cache": "artifacts/dim-research/28560655.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28", "start_char": 0, "end_char": 1823, "text_sha256": "f4d3745a4c2211551e755b314eced209ac88e072b9e02cd97cbaa5eed8303f28"} [dim-p28560655] A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. (2017). https://pubmed.ncbi.nlm.nih.gov/28560655/ DOI: 10.1007/s10549-017-4292-7
    Complete structured claim and evidence

  2. CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route.

    Human cytochrome P450 2D6 → Tamoxifen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"}
    experimental_model
    Kinetic, inhibition and recombinant-enzyme pathway mapping
    exposure
    Therapeutically relevant substrate concentrations
    limitations
    Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human liver microsomes and expressed CYPs
    plain_language
    Parent-drug removal and active-metabolite formation can move differently.
    primary_references
    [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    tissue_or_cell_type
    Sequential tamoxifen metabolism

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1013–1024

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic, inhibition and recombinant-enzyme pathway mapping · source_derived_draft · unverified_draft

    ### dim-tamoxifen-4oh CYP2D6 and other CYPs formed 4-hydroxytamoxifen through a smaller initial route. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Parent-drug removal and active-metabolite formation can move differently. organism: Human liver microsomes and expressed CYPs tissue_or_cell_type: Sequential tamoxifen metabolism experimental_model: Kinetic, inhibition and recombinant-enzyme pathway mapping limitations: Biochemical pathway identity; does not attribute the observed DIM interaction to any single CYP or prove clinical cancer outcomes. exposure: Therapeutically relevant substrate concentrations evidence_span: {"source_cache": "artifacts/dim-research/15159443.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081", "start_char": 0, "end_char": 1544, "text_sha256": "0668ce2256915fc1d4e4a5d395c544cb453e9f2599fef68f2dd5edede4f42081"} [dim-p15159443] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004). https://pubmed.ncbi.nlm.nih.gov/15159443/ DOI: 10.1124/jpet.104.065607
    Complete structured claim and evidence

  3. Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice.

    Annonacin → 4-Hydroxytamoxifen inhibition of MCF-7 cell survival source_derived_draftungraded
    Experimental context and source evidence
    dose
    Annonacin 0.1-1 micromolar with 4-hydroxytamoxifen 1 micromolar; mouse dosing in primary article
    duration
    48 hours in cells; 7-22 days in mice
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human MCF-7 cells and nude-mouse xenografts
    limitations
    Additivity in preclinical models is not evidence to combine graviola with tamoxifen; annonacin toxicity and pharmacokinetics remain limiting.
    nutrient_topic
    Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Graviola / Annona muricata
    organism
    Human MCF-7 cells and nude-mouse xenografts
    plain_language
    Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice.
    primary_references
    Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells. (2011). https://pubmed.ncbi.nlm.nih.gov/21840388/ DOI: 10.1016/j.jep.2011.07.056
    route
    In vitro and in vivo
    tissue
    Cell survival, ER-alpha signaling and xenograft size

    Graviola (Annona muricata): mechanism of action and interactions (2026-09-20) · lines 110–119

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human MCF-7 cells and nude-mouse xenografts · source_derived_draft · unverified_draft

    ## graviola-tamoxifen-additivity Annonacin and 4-hydroxytamoxifen additively reduced MCF-7 survival and estrogen-receptor transcriptional activity; annonacin also reduced MCF-7 xenograft growth in nude mice. Model/species: Human MCF-7 cells and nude-mouse xenografts Tissue/system: Cell survival, ER-alpha signaling and xenograft size Exposure: Annonacin 0.1-1 micromolar with 4-hydroxytamoxifen 1 micromolar; mouse dosing in primary article Route: In vitro and in vivo Duration: 48 hours in cells; 7-22 days in mice Limits: Additivity in preclinical models is not evidence to combine graviola with tamoxifen; annonacin toxicity and pharmacokinetics remain limiting. Primary reference: Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells. (2011). https://pubmed.ncbi.nlm.nih.gov/21840388/ DOI: 10.1016/j.jep.2011.07.056 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards