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tamoxifen (tamoxifen, Douglas)

✓ Approved

Douglas Pharmaceuticals Limited · ESR1 · Small Molecule

What is tamoxifen?

tamoxifen is a small molecule developed by Douglas Pharmaceuticals Limited. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand Namestamoxifen, Douglas
CompanyDouglas Pharmaceuticals Limited
Drug ClassSmall Molecule
Molecular TargetESR1
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Douglas Pharmaceuticals Limited

Mechanism of Action

Molecular Targets

tamoxifen acts on 1 molecular target:

ESR1estrogen receptor 1 (ER, ESR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

tamoxifen is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancer✓ Approved

Related Research Articles

PubMedAging cell2026-09-05

Midlife Growth Hormone Receptor Ablation Extends Healthy Lifespan and Induces Sex-Specific Hepatic Transcriptional Changes at Single-Cell Resolution.

Duran-Ortiz Silvana S, List Edward O EO, Young Jonathan A JA, Ikeno Yuji Y et al.

Suppression of growth hormone (GH) signaling is known to be effective to extend lifespan in mammals, yet most models rely on congenital disruption of the GH/insulin-like growth factor-1 (IGF-1) axis. Whether modulation of this pathway later in life can still influence aging and the underlying cellular mechanisms remains incompletely understood. To address this, we ablated the growth hormone receptor (Ghr) at 12-months of age in mice (12mGHRKO), using a tamoxifen-inducible model. Midlife Ghr disruption produced the expected endocrine signature of GH resistance, including reduced circulating IGF-1 and elevated GH levels. Importantly, lifespan was significantly extended in both sexes without major effects on somatic growth. Despite increased adiposity, male 12mGHRKO mice exhibited improved insulin sensitivity and protection against age-related deterioration of neuromuscular performance and bone microarchitecture. Single-nucleus RNA sequencing (snRNA-seq) of liver tissue identified a reduction of B-cells in both sexes and a dimorphic transcriptional remodeling, including a shift toward feminized gene expression in male hepatocytes, marked by reduced male-biased gene expression and increased female-biased transcriptional programs, consistent with impaired pulsatile GH-STAT5 signaling. Together, these findings demonstrate that suppression of GH signaling initiated in middle age is sufficient to reshape hepatic transcriptional programs and promote healthy longevity, supporting the GH/IGF-1 axis as a promising target for gerotherapeutic interventions.

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PubMedChemical biology & drug design2026-09-04

Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition.

Jiang Dejun D, Kwon Oh Wook OW, Joe Hanbin H, Shin Euijeong E et al.

Breast cancer is known as a frequently diagnosed malignancy in women. Over 70% of cases express estrogen receptor α (ERα). The activation of ERα promotes tumor proliferation and progression. Furthermore, mutations in ERα lead to acquired resistance against standard endocrine therapies such as tamoxifen. The induced resistance posed a significant clinical challenge in metastatic breast cancer. In this study, research for identifying novel, naturally derived compounds to inhibit the Y537S-mutated ERα was conducted using in silico methods supported by an in vitro cytotoxicity screen. Molecular docking and molecular dynamics simulations served as the primary in silico screening strategies. The top 2% of candidates were filtered from a docking screen of the IBS natural library composed of over 15,000 chemicals. From this group, 11 compounds were purchased and tested using a cell-based cytotoxicity assay in MCF-7 before advancing to detailed simulations. Five candidates were then advanced to 150 ns MD simulations. A post-MD analysis followed, including MM-PBSA binding free energy calculations and principal component analysis (PCA). The phytochemical ibs-04156 was identified as the most promising overall candidate, predicted to maintain consistent stability across both the wild-type and Y537S-mutated ERα, while ibs-18821 demonstrated potent mutant-specific inhibition via an allosteric mechanism involving spatial deviations in distal helices H3 and H11. This result shows that mutated ERα can be potentially targeted by bioactive phytochemical scaffolds found through molecular modeling, presenting a potential therapeutic strategy for metastatic breast cancer resistant to therapies such as tamoxifen.

PMID 42693657
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PubMedBMC cancer2026-09-04

Impact of adjuvant endocrine therapy on disease-free survival in early triple-positive breast cancer: a multicenter retrospective cohort study of the Turkish oncology group.

Seyyar Mustafa M, Şancı Pervin Can PC, Doğan Akif A, Biter Sedat S et al.

Triple-positive breast cancer (TPBC), characterized by concurrent ER, PR, and HER2 positivity, poses unique therapeutic challenges due to ER-HER2 crosstalk. The optimal adjuvant endocrine therapy in TPBC patients receiving anti-HER2 regimens remains poorly defined. This multicenter retrospective cohort study included 1044 early-stage TPBC patients (stage II-III) treated with neoadjuvant chemotherapy and HER2-targeted therapy between 2007 and 2024. Disease-free survival (DFS) was analyzed using Kaplan-Meier estimates and Cox regression models, with separate multivariate analyses for premenopausal (n = 474) and postmenopausal (n = 570) patients. At a median follow-up of 52 months, the 5-year DFS was 88.2% and the pCR rate was 44.3%. Residual disease was the strongest prognostic factor in both menopausal groups. In premenopausal patients, low ER expression (< 50%; HR 2.202; p = 0.003) and stage III disease (HR 2.722; p < 0.001) were independent adverse prognostic factors. Endocrine therapy type was associated with DFS on unadjusted analysis (log-rank p = 0.021) but was not significant after multivariable adjustment (adjusted overall p = 0.069). Although tamoxifen plus LHRH agonist showed a numerically higher recurrence risk than tamoxifen alone in exploratory subgroup comparison (HR 2.124; 95% CI 1.093-4.129; p = 0.026), this finding should be interpreted with caution given the non-significant overall association. In postmenopausal patients, stage III disease was the only independent adverse factor among baseline clinicopathological variables (HR 2.225; p = 0.003), and endocrine therapy type was not associated with DFS (log-rank p = 0.751; adjusted overall p = 0.614). In this large real-world TPBC cohort, residual disease was the dominant prognostic factor regardless of menopausal status. Endocrine therapy type was not independently associated with DFS after multivariable adjustment in either menopausal group. These findings are hypothesis-generating and should not guide endocrine therapy selection; prospective studies are warranted in premenopausal TPBC.

PMID 42693417
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PubMedNeoplasia (New York, N.Y.)2026-09-04

IDH3-dependent mitochondrial function in stromal fibroblasts suppresses malignant tumor growth.

Koseki Lina Rochelle LR, Kobayashi Minoru M, Ito Mai M, Nishiga Yoko Y et al.

Malignant solid tumors comprise not only cancer cells but also diverse non-cancerous stromal cells that shape the tumor microenvironment. The tricarboxylic acid (TCA) cycle has an overarching presence in providing substrates needed to drive the electron transport chain and, ultimately, ATP synthesis. However, it remains unclear which stromal cell lineages influence tumor growth through TCA-dependent mitochondrial function, and whether such activities act in a tumor-promoting or tumor-suppressive manner. Isocitrate dehydrogenase 3 (IDH3), a rate-limiting TCA cycle enzyme that generates NADH to support mitochondrial respiration, provides a genetic entry point to interrogate mitochondrial TCA-dependent function in stromal cells. In this study, we established a mouse model in which tamoxifen administration induces CreERT2-dependent knockout of the α subunit of IDH3 (IDH3α) in all somatic cells. Using this model with transplantation of Idh3a-intact murine cancer cells, we found that host Idh3a deficiency accelerated growth of murine MC38 tumors in a cancer cell line-dependent manner. Bone marrow chimera experiments indicated that hematopoietic lineages were not responsible for this phenotype, suggesting a contribution from tissue-resident non-hematopoietic stromal cells that are not replaced by bone marrow transplantation. Single-cell RNA sequencing of human tumor specimens revealed broad IDH3A expression across multiple tumor microenvironment compartments, including fibroblasts. Consistently, in vitro co-culture assays demonstrated that Idh3a-intact, but not Idh3a-KO, fibroblasts suppressed cancer cell proliferation in a contact-dependent manner. Together, these findings identify IDH3α-dependent mitochondrial function in fibroblasts as a critical determinant of tumor progression and suggest that stromal mitochondrial metabolism represents an important axis for modulating tumor behavior.

PMID 42697150
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PubMedJournal of advanced pharmaceutical technology & research2026-09-03

Nanovesicle-formulated Sterculia coccinea Jack (hantap) leaf extract: Estrogen receptor-alpha molecular docking and cytotoxicity in Michigan Cancer Foundation-7 cells.

Susanto Yuliet Y, Khaerati Khildah K, Sharon Nela N, Patala Recky R et al.

Sterculia coccinea Jack (hantap) is an Indonesian medicinal plant with limited evidence of anticancer activity. The objective of this study was to identify the phytochemical components of hantap leaf extract, evaluate its interaction with estrogen receptor-alpha (ER-α) through molecular docking, and develop nanoliposome formulations to improve its physicochemical properties. The extract yield was 15.7%, and the phytochemical profile was characterized using liquid chromatography-high-resolution mass spectrometry. Molecular docking against ER-α was performed using tamoxifen as the reference ligand. Nanoliposomes were prepared by thin-film hydration using phosphatidylcholine and cholesterol at ratios of 0.6:0.3 (F1), 0.9:0.3 (F2), and 1.2:0.3 (F3). The formulations showed particle sizes of 158.3 ± 1.59 nm, 148.23 ± 2.68 nm, and 157.3 ± 1.10 nm; zeta potentials of - 30.16 ± 1.40 mV, -31.61 ± 0.16 mV, and - 32.84 ± 0.31 mV; and polydispersity index values of 0.28 ± 0.02, 0.29 ± 0.03, and 0.23 ± 0.02 for F1, F2, and F3, respectively. Entrapment efficiency for total phenolics ranged from 94.43% to 97.04%, while total flavonoid entrapment ranged from 32.84% to 73.54%. Docking analysis showed that linarin and apigenin had stronger binding affinity to ER-α than tamoxifen. Based on physicochemical evaluation, F2 was selected as the optimal formulation and showed weak cytotoxic activity against Michigan Cancer Foundation-7 (MCF-7) cells in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, with an IC50 value of 282.06 ± 3.39 μg/mL. In conclusion, hantap leaf extract nanoliposomes exhibited favorable nanoscale characteristics, while their cytotoxic effect against MCF-7 cells remained weak under the tested conditions.

PMID 42689295
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PubMedResearch square2026-09-03

Hydroxychloroquine-Induced Retinopathy in Systemic Lupus Erythematosus: Predictors of Progression Following Drug Discontinuation.

Gutowski Emily E, Modi Yasha Y, Velez Alfredo Gutierrez AG, Colcombe Joseph J et al.

Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) management. However, the medication can accumulate within organs and cause toxicity including retinopathy. HCQ is usually discontinued once ocular toxicity is diagnosed, but this is not always sufficient to avoid further damage. Whether retinal injury progresses following HCQ cessation, and which patients are at risk, is of great interest. Prior studies examining progression after HCQ discontinuation are sparse and limited by small sample sizes, and none specifically examine patients with SLE. This study aimed to identify predictors of progression of HCQ-induced retinopathy in SLE patients after medication discontinuation. We queried the NYU Lupus Cohort to identify patients with documented HCQ-induced retinopathy who discontinued HCQ and had at least one optical coherence tomography (OCT) follow-up to assess for progression. Demographic information, cumulative HCQ dose, duration of therapy, presence of chronic kidney disease or tamoxifen use, SLE disease activity, and ophthalmologic follow-up intervals were collected. Two ophthalmologists independently reviewed OCT and Humphrey visual field data to confirm retinopathy, grade its severity, and determine progression following drug discontinuation. Statistical analysis was performed using Student's t-test or Wilcoxon rank-sum test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Twenty-one patients with confirmed HCQ retinopathy were included. The mean duration of HCQ therapy preceding diagnosis was 16.2 years and the mean cumulative exposure was 1884 g. Retinal toxicity progressed in 6 patients (28.6%) despite HCQ discontinuation. There appeared to be a trend towards a greater likelihood of progression with more severe retinal toxicity at the time of diagnosis. However, there were no differences between progressors and non-progressors with respect to age at diagnosis, duration or cumulative HCQ exposure, SLE disease activity, tamoxifen use, chronic kidney disease, or guideline-concordant care. Nearly thirty percent of patients with SLE and HCQ retinopathy progressed despite drug discontinuation. No baseline clinical predictors were associated with progression, though there was a descriptive trend toward greater risk with more severe baseline retinopathy. These data emphasize the importance of continued ocular surveillance for progression of toxicity after discontinuation.

PMID 42687909
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