Endoxifen is a non-steroidal triphenylethylene selective estrogen receptor modulator (SERM) and the active secondary metabolite of tamoxifen. It is not FDA-approved and remains investigational, studied in multiple Phase 1 and Phase 2 human trials for endocrine-refractory ER-positive breast cancer, desmoid tumors, and other hormone-receptor-positive solid tumors. Endoxifen is sold by research-chemical suppliers labeled for laboratory use only, not for human consumption.
Mechanism of Action
Endoxifen exerts dual mechanisms: (1) ER-alpha antagonism—binds estrogen receptor alpha at nanomolar concentrations, blocks estrogen-stimulated transcription, and uniquely promotes proteasomal degradation of ER-alpha in MCF7 breast cancer cells in vitro, unlike tamoxifen or 4-hydroxytamoxifen. (2) At clinically relevant concentrations, endoxifen inhibits protein kinase C beta-1 (PKC-beta-1), induces PKC-beta-1 degradation, reduces PKC-beta-1-driven AKT Ser473 phosphorylation, and induces apoptosis in ER-alpha-positive breast cancer cells in vitro—proposed as an ER-alpha-independent second mechanism.
Research Summary
No FDA approval or approval in any jurisdiction; endoxifen is investigational only. Human trials: Goetz et al. 2017 Phase 1 in endocrine-refractory metastatic ER-positive breast cancer (20–160 mg/day oral, no maximum tolerated dose, 3 partial responses, clinical benefit rate 26.3%); Takebe et al. 2021 Phase 1 in gynecologic, desmoid, and hormone-receptor-positive solid tumors (20–360 mg/day, no MTD, partial responses in desmoid tumors); Alliance A011203 randomized Phase 2 found Z-endoxifen not superior to tamoxifen overall but showed PFS benefit in CDK4/6-inhibitor-naive patients (HR 0.42). Preclinical: in ovariectomized mice, oral Z-endoxifen increased cancellous and cortical bone mass; in rats, reduced bone turnover and protected against bone loss; in MCF7 xenografts, showed superior antitumor activity versus tamoxifen, letrozole, and exemestane.
Verified testing for Endoxifen
Aggregated from 2 lab-verified Certificates of Analysis uploaded directly by labs. Purity averages exclude values outside [50%, 100%] to filter unit-misreads.
Scored vendors carrying Endoxifen, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.
No validated human dosing regimen outside clinical trials
Plausible SERM-class risks (thromboembolic, endometrial, ocular) inferred from tamoxifen; endoxifen-specific adverse-event profile not cataloged in sourced literature
Unapproved in all jurisdictions; marketed products are unregulated
Sold by vendors labeled 'not for human consumption'
First-in-Human Phase I Study of the Tamoxifen Metabolite Z-Endoxifen in Women With Endocrine-Refractory Metastatic Breast Cancer. 2017. PMID 28854070.
Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors. 2021. PMID 33659039.
Tamoxifen Citrate or Z-Endoxifen Hydrochloride in ER-Positive, HER2-Negative Breast Cancer (Alliance A011203). 2019.
Frequently asked questions
Has Endoxifen been independently lab-tested?
Disclosed Labs has collected 2 Certificates of Analysis (COA) for Endoxifen from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.5% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/endoxifen/testing.
Where can researchers source Endoxifen?
1 vendor with Disclosed Labs trust grades currently list Endoxifen, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/endoxifen.
How does Endoxifen work?
Endoxifen exerts dual mechanisms: (1) ER-alpha antagonism—binds estrogen receptor alpha at nanomolar concentrations, blocks estrogen-stimulated transcription, and uniquely promotes proteasomal degradation of ER-alpha in MCF7 breast cancer cells in vitro, unlike tamoxifen or 4-hydroxytamoxifen. (2) At clinically relevant concentrations, endoxifen inhibits protein kinase C beta-1 (PKC-beta-1), induces PKC-beta-1 degradation, reduces PKC-beta-1-driven AKT Ser473 phosphorylation, and induces apoptosis in ER-alpha-positive breast cancer cells in vitro—proposed as an ER-alpha-independent second mechanism.
What does the research say about Endoxifen?
No FDA approval or approval in any jurisdiction; endoxifen is investigational only. Human trials: Goetz et al. 2017 Phase 1 in endocrine-refractory metastatic ER-positive breast cancer (20–160 mg/day oral, no maximum tolerated dose, 3 partial responses, clinical benefit rate 26.3%); Takebe et al. 2021 Phase 1 in gynecologic, desmoid, and hormone-receptor-positive solid tumors (20–360 mg/day, no MTD, partial responses in desmoid tumors); Alliance A011203 randomized Phase 2 found Z-endoxifen not superior to tamoxifen overall but showed PFS benefit in CDK4/6-inhibitor-naive patients (HR 0.42). Preclinical: in ovariectomized mice, oral Z-endoxifen increased cancellous and cortical bone mass; in rats, reduced bone turnover and protected against bone loss; in MCF7 xenografts, showed superior antitumor activity versus tamoxifen, letrozole, and exemestane.
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