Biological Activity

Bioactivity / Mechanism

In engineered ERβ-expressing MCF7, Hs578T and U2OS cells, Z-endoxifen increased ERβ protein abundance after 24 hours. The authors describe this response as receptor stabilization. The assay does not measure receptor half-life or establish that this protein response causes growth inhibition. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

In Vitro Studies

In an eight-day MCF7 growth assay with 1 nM estradiol, ERβ-expressing clones were more sensitive to 20–40 nM Z-endoxifen than parental ERβ-negative cells. Higher concentrations (100–1,000 nM) reduced the parental-cell response. The low-dose effect varied by clone; these treatment concentrations are not IC50 values. [1]

ERβ protein response to endoxifen

Cell-based study · Engineered MCF7-ERβ and Hs578T-ERβ breast cancer cells; U2OS-ERβ validation cells. [1]

After 24 h, endoxifen increased ERβ protein abundance in all three ERβ-expressing cell models. The authors describe this as receptor stabilization; no receptor half-life or causal link to growth inhibition was measured in this assay.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
ERβ abundance relative to vehicle, with tubulin loading control	Reported qualitative result Increased ERβ signal after endoxifen exposure; no numerical fold change adopted.	[1]

Literature-Reported Treatment Conditions

Treatment concentration: 20, 40, 100 and 1,000 nM
Exposure duration: 24 h
Method: Cell treatment followed by Western blotting
Vehicle: Vehicle control included; chemical composition not specified in the cited methods.
Reported limits: No quantitative densitometry or replicate count supplied for the adopted blots.

Methods and source locations

Compound reported in the paper: (Z)-Endoxifen; Compound label in the paper: Z-endoxifen

Results concern the reported experimental Z-endoxifen material and model; they do not establish lot-specific performance or clinical efficacy.

Figure 2 and caption; Results: ERβ protein levels are stabilized by endoxifen; Methods: cell culture and Western blotting

ERβ abundance relative to vehicle, with tubulin loading control: Western blot after 24 h; 20, 40, 100 and 1,000 nM endoxifen. — Figure 2A–C and caption; Results: ERβ protein levels are stabilized by endoxifen

ERβ expression increases sensitivity to endoxifen in MCF7 cells

Cell-based study · Parental ERβ-negative MCF7 compared with two ERβ-expressing clones (#1 and #3). [1]

Endoxifen inhibited estradiol-stimulated growth more strongly at low concentrations in ERβ-expressing clones than in parental MCF7 cells. The low-dose effect varied by clone: the significance marker at 20 nM is displayed for clone #3, while both clones show inhibition at 40 nM. Parental cells were less responsive at these low concentrations.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Eight-day cell growth relative to vehicle under 1 nM estradiol	Reported qualitative result ERβ clones showed greater inhibition at 20–40 nM than parental cells, with clone-dependent significance. Higher concentrations (100–1,000 nM) reduced the parental-cell response; no complete-blockade threshold is assigned from the graph.	[1]

Literature-Reported Treatment Conditions

Treatment concentration: 20–1,000 nM endoxifen with 1 nM estradiol
Exposure duration: 8 days; medium/treatment replaced every other day
Method: CellTiter-Glo growth/viability assay in phenol-red-free medium with 10% triple charcoal-stripped FBS
Vehicle: Vehicle and estradiol-only controls; vehicle composition not specified.
Co-treatment: Estradiol challenge; no other antiestrogen co-treatment in this experiment.
Reported limits: Exact biological/technical replicate count and error-bar definition for Figure 5 are not specified in its caption; no IC50 is reported/adopted.

Methods and source locations

Compound reported in the paper: (Z)-Endoxifen; Compound label in the paper: Z-endoxifen

Results concern the reported experimental Z-endoxifen material and model; they do not establish lot-specific performance or clinical efficacy.

Figure 5 and caption; Methods: cell proliferation assays; Results: Endoxifen’s ability to inhibit estrogen induced gene expression and proliferation is enhanced by ERβ; Additional file 2

Eight-day cell growth relative to vehicle under 1 nM estradiol: CellTiter-Glo luminescent viability readout; vehicle and estradiol-only controls; Figure 5 significance symbols use ANOVA, P < 0.05. — Figure 5 and caption; Results paragraph beginning “To confirm these data”

In Vivo Studies

Oral Z-endoxifen reduced tumor-growth AUC in AI-sensitive and letrozole-resistant breast-cancer xenografts. In the sensitive model, 75 mg/kg daily outperformed tamoxifen and letrozole, whereas the 25 mg/kg comparison with letrozole was not significant. In the resistant model, 50 mg/kg given five days per week outperformed letrozole and exemestane but was not significantly different from fulvestrant or exemestane plus everolimus. Lower body weight accompanied the higher-dose sensitive-model regimen and the resistant-model regimen. [2]

Antitumor activity did not generalize to a subcutaneous CRT435 glioblastoma xenograft study. Endoxifen at 25, 50 or 75 mg/kg orally, alone or with temozolomide, showed no significant tumor-volume benefit in the authors’ Day-16 comparison. Treatment was planned for 28 days, but attrition limits interpretation of later mean curves. This model does not establish intracranial efficacy. [3]

Growth inhibition in AI-sensitive breast cancer xenografts

Animal study · Four- to six-week-old ovariectomized female BALB/c athymic nude mice bearing MCF7AC1 aromatase-expressing breast xenografts; estrogen pellets supplied. [2]

Both Z-endoxifen doses reduced baseline-adjusted tumor-growth AUC versus untreated control and tamoxifen. The 75 mg/kg dose also outperformed letrozole; the 25 mg/kg comparison with letrozole was not significant. The 75 mg/kg group had lower body weight at four weeks.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Baseline-adjusted tumor volume AUC through four weeks	Between-group AUC comparison 75 mg/kg: versus control p < 0.0001, tamoxifen p < 0.0001, letrozole p = 0.0005. 25 mg/kg: versus control p < 0.0001, tamoxifen p = 0.002, letrozole p = 0.10.	[2]
Body weight at four weeks	Reported qualitative result 75 mg/kg group had significantly lower body weight than control, tamoxifen, letrozole and 25 mg/kg groups.	[2]

Conditions shared by the study groups

Route: Oral gavage
Frequency: Once daily
Treatment course: 4 weeks
Vehicle: PEG400 to ascorbic acid 50:50

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Z-endoxifen 25 mg/kg	No-drug control (analyzed n = 28); tamoxifen 500 μg/day s.c. (n = 30); letrozole 10 μg/day s.c. (n = 29). Comparator suspensions: 0.3% hydroxypropyl cellulose.	Lower AUC than control/tamoxifen; comparison with letrozole not significant (p = 0.10).	[2]
Z-endoxifen 75 mg/kg	Same control and comparator groups as the 25 mg/kg arm.	Lower AUC than control, tamoxifen and letrozole, accompanied by lower body weight.	[2]

Z-endoxifen 25 mg/kg: Model: MCF7AC1 xenografts; 30 mice/group randomized; analyzed Z-endoxifen n = 27.

Z-endoxifen 75 mg/kg: Model: MCF7AC1 xenografts; 30 mice/group randomized; analyzed Z-endoxifen n = 26.

Methods and source locations

Compound reported in the paper: (Z)-Endoxifen; Compound label in the paper: Z-endoxifen

Results concern the reported experimental Z-endoxifen material and model; they do not establish lot-specific performance or clinical efficacy.

Figure 1a–b; Methods: Cell line xenograft models and Statistical analysis; Results Sec12 first paragraph; Additional file 1

Baseline-adjusted tumor volume AUC through four weeks: Weekly caliper measurements; AUC per mouse by trapezoid method, Wilcoxon rank-sum comparisons. Longitudinal plots: mean ± SEM. — Results Sec12 first paragraph; Figure 1a–b and caption

Body weight at four weeks: Viewed supplementary boxplot and caption; Wilcoxon rank-sum tests; no numerical weights inferred. — Additional file 1 Figure S1; Results Sec12 first paragraph

Z-endoxifen 25 mg/kg · Figure 1a–b; Methods: Cell line xenograft models and Statistical analysis; Results Sec12 first paragraph; Additional file 1

Z-endoxifen 75 mg/kg · Figure 1a–b; Methods: Cell line xenograft models and Statistical analysis; Results Sec12 first paragraph; Additional file 1

Comparator activity in letrozole-resistant breast xenografts

Animal study · Six- to seven-week-old ovariectomized female athymic nude mice bearing MCF7LR xenografts; randomized n = 12 mice/group. [2]

In the separately implanted letrozole-resistant cohort, 50 mg/kg Z-endoxifen reduced tumor-growth AUC versus letrozole and exemestane, but was not significantly different from fulvestrant or exemestane plus everolimus. Lower body weight occurred; the authors report dietary Nutrical supplementation helped control weight loss.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Baseline-adjusted tumor volume AUC through 63 days	Between-group AUC comparison Z-endoxifen versus letrozole p < 0.001; versus exemestane p = 0.03; versus exemestane plus everolimus p = 0.93; versus fulvestrant p = 0.29.	[2]
Body weight at 63 days	Reported qualitative result Z-endoxifen group had lower body weight than each comparator group in the supplementary plot.	[2]

Conditions shared by the study groups

Route: Oral gavage
Frequency: 5 days/week
Treatment course: AUC endpoint 63 days; longitudinal follow-up through 23 weeks

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Z-endoxifen 50 mg/kg	Letrozole 10 μg/day (resistant-model control), fulvestrant 1000 μg/day, exemestane 250 μg/day, or exemestane plus oral everolimus 2.5 mg/day, as printed. Endocrine comparators administered s.c.; all groups received androstenedione.	Lower AUC than letrozole and exemestane; no significant difference from fulvestrant or exemestane plus everolimus. Weight loss required nutritional management.	[2]

Z-endoxifen 50 mg/kg: Model: MCF7LR xenografts; n = 12 mice/group randomized.; Reported limits: Vehicle for Z-endoxifen in this second cohort not separately specified.

Methods and source locations

Compound reported in the paper: (Z)-Endoxifen; Compound label in the paper: Z-endoxifen

Results concern the reported experimental Z-endoxifen material and model; they do not establish lot-specific performance or clinical efficacy.

Figure 1c–d; Methods: Cell line xenograft models and Statistical analysis; Results Sec12 third paragraph; Additional file 3

Baseline-adjusted tumor volume AUC through 63 days: Weekly tumor measurements and mouse-level AUC, Wilcoxon rank-sum tests; longitudinal volume curves shown as mean ± SEM. — Figure 1c–d; Results Sec12 paragraph beginning “Given the promising antitumor activity”

Body weight at 63 days: Viewed weight boxplot and caption; Wilcoxon rank-sum comparisons; no exact weight estimates adopted. — Additional file 3 Figure S3; Results Sec12 third paragraph

Z-endoxifen 50 mg/kg · Figure 1c–d; Methods: Cell line xenograft models and Statistical analysis; Results Sec12 third paragraph; Additional file 3

No significant benefit in the CRT435 GBM xenograft comparison

Animal study · Female athymic nude mice, 6–12 weeks old, with subcutaneous CRT435 patient-derived GBM xenografts. [3]

Endoxifen monotherapy or combinations with temozolomide did not produce a statistically significant tumor-volume benefit in the authors’ comparison. Analysis used Day 16 to retain sample size; treatment was planned for 28 days, with humane-endpoint attrition. Later group means therefore do not establish a durable response. This subcutaneous model does not test intracranial efficacy or blood–brain barrier penetration.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Tumor volume under endoxifen alone or with temozolomide	Reported between-group result No significant between-group treatment differences identified through Day 16; a time × treatment interaction was significant, F (35, 189) = 2.609, p < 0.001. The interaction is not evidence of efficacy versus vehicle.	[3]

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Endoxifen monotherapy dose-ranging cohorts 25, 50 or 75 mg/kg (separate cohorts)	Vehicle control and TMZ-only 25 mg/kg comparator.	No significant tumor-volume benefit identified in the authors’ comparison; no efficacy conclusion from late mean-curve separation.	[3]
Endoxifen plus temozolomide cohorts Endoxifen 25, 50 or 75 mg/kg with TMZ 25 mg/kg	Vehicle, TMZ alone and corresponding endoxifen monotherapy cohorts.	No significant tumor regression benefit versus vehicle; synergy was not demonstrated in vivo.	[3]

Endoxifen monotherapy dose-ranging cohorts: Model: CRT435 subcutaneous PDX; Results n = 6/group, Methods 6–8/group.; Route: Oral; Frequency: Once daily; Treatment course: 28 days planned; Day-16 inferential comparison; Vehicle: Vehicle control composition as above; no separate endoxifen formulation specified.; Reported limits: Unresolved reporting ambiguity in initial n; time-specific denominators not tabulated.

Endoxifen plus temozolomide cohorts: Model: Same CRT435 PDX experiment.; Route: Endoxifen oral; TMZ intratumoral (source-reported); Frequency: Endoxifen daily; TMZ 5 days on/2 off; Treatment course: 28 days planned; four TMZ cycles (20 doses); Day-16 comparison; Vehicle: Vehicle control composition as above.; Reported limits: Initial n discrepancy and attrition limit precision.

Methods and source locations

Compound reported in the paper: (Z)-Endoxifen; Compound label in the paper: Z-endoxifen

Results concern the reported experimental Z-endoxifen material and model; they do not establish lot-specific performance or clinical efficacy.

Figure 7; Supplementary Material 1 Figure 8A–H; Methods Sec15–16; Results Sec24; Discussion model limitations

Tumor volume under endoxifen alone or with temozolomide: Caliper tumor volumes; mixed-effects model with Dunnett comparisons. Mean tumor volume ± SE in Figure 7; individual trajectories in Supplementary Figure 8. — Methods Sec16; Results Sec24; Figure 7; Supplementary Figure 8A–H

Endoxifen monotherapy dose-ranging cohorts · Figure 7; Supplementary Material 1 Figure 8A–H; Methods Sec15–16; Results Sec24; Discussion model limitations

Endoxifen plus temozolomide cohorts · Figure 7; Supplementary Material 1 Figure 8A–H; Methods Sec15–16; Results Sec24; Discussion model limitations

Specifications

Manufacturer	Adooq Bioscience
Actions	Antagonist
CAS Number	112093-28-4
Applications	Estrogen receptor antagonist
Formula	C₂₅H₂₇NO₂
Molecular Weight	373.49
SMILES	CCC(=C(C1=CC=C(C=C1)O)C2=CC=C(C=C2)OCCNC)C3=CC=CC=C3

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Wu X, Subramaniam M, Grygo SB, et al. Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen. Breast cancer research : BCR (2011). PMID: 21392396 DOI: 10.1186/bcr2844 Source material
[2] Jayaraman S, Hou X, Kuffel MJ, et al. Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer. Breast cancer research : BCR (2020). PMID: 32430040 DOI: 10.1186/s13058-020-01286-7 Source material
[3] Shneyderman A, Hammer SS, Remmel HL, et al. Evaluation of (Z)-endoxifen as a potential therapy for glioblastoma multiforme through computational and experimental analyses. Scientific reports (2025). PMID: 41173946 DOI: 10.1038/s41598-025-22034-x Source material

Publications

2 publications citing this product

Marina Arino Martin, .et al. , Environ Res, 2021, Apr 3;197:111121 PMID: 33823193
Martin MA, .et al. , Water Res, 2019, Dec 29;171:115451 PMID: 31901682

Documents & Downloads

Endoxifen (Z-isomer)

Publications for Endoxifen (Z-isomer)

Select a Size

Package Sizes

DMSO Solution