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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

PubMedbioRxiv : the preprint server for biology2026-07-17

Tracing developmental and adult hematopoiesis with an endogenous zebrafish runx1-2A-CreERT2 CRISPR knock-in.

Preston James A JA, Usha Masuma K MK, Ekker Stephen C SC, Clark Karl J KJ et al.

Zebrafish combines the power of genetics and unparalleled in vivo imaging for investigating the dynamics of vertebrate hematopoietic development. Across species, the transcription factor Runx1 is essential for definitive hematopoiesis. We generated a zebrafish runx1-2A-creERT2 CRISPR knock-in for tamoxifen-regulated Cre recombinase Runx1 lineage tracing and characterized its activity using the ubi:Switch recombinase-dependent fluorescence reporter, microscopic live imaging and flow cytometry. Tamoxifen treatment beginning at gastrula stage labeled all expected Runx1 lineages in the early embryo, including neuroectodermal olfactory placode and Rohan-Beard neurons, primitive hematopoietic blood cells, and nascent hematopoietic stem and progenitor cells (HSPCs) in the dorsal aorta. Runx1 HSPCs colonized the larval caudal hematopoietic tissue and thymus from three to five days of development. Timed tamoxifen induction of Cre activity allowed separation of Runx1 primitive hematopoiesis from definitive HSPC emergence and larval stem cell niche colonization. Flow cytometry of kidney marrow and peripheral blood from adults treated with tamoxifen at gastrula stage revealed Runx1 embryonic hematopoietic cells contributed to adult hematopoietic precursors, myeloid, lymphoid, and peripheral blood lineages. Labeling of all blood lineages was also effective by tamoxifen treatment of 5-month-old adults. The zebrafish runx1-2A-creERT2 line provides a powerful tool for precise spatial and temporal analysis of Runx1 progenitor mechanisms in developmental and adult hematopoiesis. zebrafish endogenous runx1-2A-creERT2 provides inducible Cre recombinase genetic analysis in all runx1 neuromesodermal and blood lineages zebrafish runx1-2A-creERT2 line enables in vivo spatial and temporal analysis of embryonic and adult hematopoiesis.

PMID 42465524
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PubMedMedical oncology (Northwood, London, England)2026-07-17

Formulation development and preliminary biological evaluation of a menthol modified thermoresponsive tamoxifen sol-gel.

Faheem Saleha S, Hameed Huma H, Al-Hussain Sami A SA, Irfan Ali A et al.

Localized drug delivery strategies offer potential advantages in improving therapeutic concentration at tumor sites while minimizing systemic exposure. In this study, a thermoresponsive poloxamer based sol-gel system incorporating tamoxifen citrate with L-menthol was developed and characterized for potential intratumoral application. The formulation was prepared using the cold method and optimized through response surface methodology\. The optimized system exhibited rapid sol-gel transition at 38.5 °C with gelation time around 37s, acceptable syringeability, pH compatibility with mildly acidic tumor conditions, and uniform drug content (93-96%) with high encapsulation efficiency (88-93%). In vitro release studies demonstrated sustained tamoxifen release over 48 h, best described by the Korsmeyer-Peppas model (n = 0.366), indicating diffusion-controlled release. Physicochemical analyses (FTIR, DSC, XRD, SEM) confirmed drug excipient compatibility and partial amorphization within the polymeric matrix. Molecular docking provided preliminary insight into potential interactions with breast cancer associated proteins. In vitro cytotoxicity in MCF-7 cells showed reduced IC₅₀ values for the menthol containing formulation compared to tamoxifen alone. Acute toxicity evaluation in mice indicated acceptable short-term tolerability. Overall, this system represents a promising localized delivery platform warranting further mechanistic and in vivo efficacy investigations.

PMID 42467342
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PubMedScientific reports2026-07-17

Loss of p130Cas/Bcar1 impairs palatal mesenchymal expansion and causes cleft palate.

Han Tao T, Gao Jing J, Wu Wei W, Nakatomi Mitsushiro M et al.

Palatogenesis is a complex developmental process that requires the coordinated growth, elevation, and fusion of palatal shelves. Disruption of these events results in cleft palate, which is one of the most common congenital, craniofacial anomalies. p130Crk-associated substrate (p130Cas), also known as breast cancer anti-estrogen resistance 1 (BCAR1), is an adaptor protein involved in integrin-mediated signaling and cytoskeletal regulation; however, its role in late embryonic development is poorly understood because global p130Cas-deficiency leads to early embryonic lethality. In the present study, tamoxifen-inducible conditional knockout mice were used to investigate the role of p130Cas in palatal development. Conditional deletion of p130Cas resulted in cleft palate, characterized by impaired horizontal growth of the palatal shelves. Reduced mesenchymal cell proliferation within the palatal shelves was confirmed using Ki-67 immunostaining and EdU incorporation assays. Primary mouse embryonic palatal mesenchymal (MEPM) cells derived from p130Cas-deficient embryos consistently exhibited impaired proliferation and migration in vitro. The epithelial-specific deletion of p130Cas did not result in cleft palate, indicating that p130Cas function in the palatal mesenchyme is critical for normal palatal development. Taken together, these findings indicate that p130Cas is an important regulator of palatal mesenchymal expansion during secondary palatogenesis. The impaired proliferative growth of the palatal mesenchyme likely underlies the developmental basis of cleft palate in this model.

PMID 42463749
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PubMedFrontiers in immunology2026-07-17

Stem cell factor 248 shapes ILC2 transcriptional programs and promotes mucosal inflammation in allergic asthma.

Asai Nobuhiro N, Lombardo Grace K GK, Ocadiz-Ruiz Ramon R, Gu Yao Y et al.

Stem cell factor (SCF), also known as Kit ligand, is a pleiotropic cytokine that signals through the c-Kit receptor to regulate cellular development, survival, and proliferation. Although SCF is classically recognized for its essential role in hematopoiesis and mast cell biology, c-Kit is also expressed by innate lymphoid cell progenitors (ILCp) and subsets of mature innate lymphoid cells (ILCs), suggesting broader immunoregulatory functions. Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 airway inflammation and serve as an important source of type 2 cytokines during allergic responses. We previously demonstrated increased expression of the pro-inflammatory SCF248 isoform in the lungs of mice with chronic allergic inflammation, while elevated soluble SCF levels have also been reported in patients with asthma. In the present study, we further observed that SCF248 is upregulated in the bone marrow during allergic inflammation, suggesting that SCF248 may contribute to both local and systemic regulation of allergic immune responses. To define the role of SCF/c-Kit signaling in ILC2 biology, we first performed transcriptional profiling of SCF-deficient ILC2s, which revealed reduced expression of genes associated with cytokine signaling, activation, and effector function, including Il4, Stat5b, and PI3K-AKT pathway components, consistent with impaired inflammatory responsiveness. Mechanistically, pro-inflammatory and type 2 cytokines induced SCF248 expression in mesenchymal cells in vitro. To define its functional impact, ILC progenitors were cultured on OP9-DL1 stromal cells with upregulated SCF248 expression, which increased expression of ILC2-associated markers and the maturation program, supporting a role for SCF248 in enhancing ILC2 maturation and activation. In vivo validation using tamoxifen-inducible whole-body SCF-deficient mice (SCFfl/fl ; UBC-CreERT2) in an Alternaria alternata model of allergic airway inflammation demonstrated that SCF deficiency reduced SCF248 expression, attenuated type 2 cytokine production, diminished lung inflammation, and decreased circulating and pulmonary ILC2 populations. Similarly, SCF248 blockade reduced allergic inflammation and altered bone marrow ILC compartments. Together, these findings identify SCF248 as a regulator of ILC2 maturation and activation, amplifying mucosal type 2 inflammation during allergic airway disease.

PMID 42465746
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PubMedbioRxiv : the preprint server for biology2026-07-17

Diet-Induced Obesity Exacerbates Helicobacter pylori -Associated Precancerous Phenotypes.

Zhao Xuyao X, Wojcicki Nicholas N, Kim Kee-Hong KH, Lanman Nadia Atallah NA et al.

Stomach infection with the bacterium Helicobacter pylori ( Hp ) can cause chronic gastric inflammation, metaplasia (transdifferentiation of mature cell types), dysplasia (abnormal cells), and finally cancer. Obesity can also increase gastric cancer risk. However, host- Hp interactions during obesity are poorly understood. Here we investigated the impact of diet-induced obesity in two mouse models of Hp -associated disease. To model chronic gastric inflammation, we used C57BL/6 mice, and to model more severe disease, we used transgenic mice in which tamoxifen induces gastric expression of a constitutively active Kras allele, leading to metaplasia. We fed mice a high-fat diet (60% kilocalories from fat) to induce obesity, or a matched control diet (10% kilocalories from fat), then infected them with Hp or mock-infected them. In mock-infected C57BL/6 mice, high-fat diet had a minimal impact on gastric pathology and gene expression. In Hp -infected C57BL/6 mice, high-fat diet increased inflammation at the junction between the glandular stomach and non-glandular forestomach, a squamous epithelium similar to the human esophagus, and increased gastric expression of the cancer-associated genes Cldn7 and Reg3g . In KRAS+ mice with or without Hp infection, the impact of diet-induced obesity was more apparent, with increased metaplasia and dysplasia (abnormal cells). As well, high-fat diet caused an expansion of metaplastic pit cells, a lineage we previously found to be associated with Hp -driven inflammation. Thus, in these mouse models, diet-induced obesity does not directly drive gastric immunopathology, but enhances the development of pre-cancerous changes under susceptible conditions. Most gastric cancers are caused by stomach infection with the bacterium Helicobacter pylori . However, most infected individuals never develop cancer. Therefore, additional risk factors must tip the balance toward gastric cancer development. Obesity, or excessive body fat accumulation that poses a risk to health, is associated with gastric cancer development. However, specific mechanisms for obesity-driven gastric cancer risk are not well defined. Here we tested the hypothesis that obesity would exacerbate Helicobacter pylori -associated disease phenotypes using two clinically relevant mouse models. In wild-type mice, obesity induced by a very high-fat diet had a minimal impact on the stomach in the absence of infection, but increased the expression of some cancer-associated genes during infection. However, in mice with genetically driven pre-cancer, diet-induced obesity exacerbated the disease pathology, especially in infected mice. Therefore, obesity's impact on gastric cancer risk may be more evident in the later stages of the disease.

PMID 42465293
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PubMedbioRxiv : the preprint server for biology2026-07-17

E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.

Yi Dan D, Tripathi Ankit A, Zheng Qi Q, Liu Bin B et al.

Pulmonary arterial hypertension (PAH) is driven by maladaptive endothelial remodeling, but the transcriptional regulators that couple proliferative stress to arterialized endothelial states remain incompletely defined. E2F transcription factor 1 (E2F1) is classically viewed as a cell-cycle regulator; whether E2F1 functions as a disease-driving node that promotes endothelial arterial programming in PAH remains unknown. We integrated human PAH lung transcriptomic analyses, deconvolution-based endothelial-state scoring, and complementary mouse and rat PH models with bulk RNA-seq, single-cell RNA-seq, pseudotime analysis, and CellChat inference. E2F1 function was tested using adenoviral E2F1 overexpression, pharmacological pan-E2F inhibition with HLM006474, and genetic E2f1 loss on a tamoxifen-inducible endothelial Egln1 -deletion background. In PAH lungs, E2F1 was increased and arterial endothelial cell (AEC) fraction and expanded arterial program scores were elevated. Similarly, Egln1 Tie2Cre lungs showed increased E2F1, induction of arterial remodeling genes, and activation of an E2F target program. Genetic loss of E2f1 reduced right ventricle systolic pressure, right ventricle hypertrophy, vascular remodeling, and distal muscularization in Egln1 -driven PH mice model. Bulk RNA-seq showed suppression of E2F, mitotic, epithelial mesenchymal transition, and extracellular matrix-remodeling programs. Single-cell RNA-seq showed reduced AEC accumulation, normalized CAP1/CAP2 distribution, and reduced progression along the CAP1-AEC trajectory. CellChat analysis identified loss of an arterial communication hub, including reduced ECM, VEGF, and Notch signaling when E2F1 is loss. Conversely, E2F1 overexpression in human lung microvascular ECs increased proliferation, activated E2F/cell-cycle and Notch/arterial programs. Pharmacological inhibition of E2F via HLM006474 suppressed endothelial proliferation and attenuated Egln1 -driven and MCT-induced PH, including reversal of established MCT-PH. E2F1 acts as a disease-relevant transcriptional factor linking endothelial cell-cycle activation to arterial programming, matrix and angiogenic communication programs, and pulmonary vascular remodeling. Genetic or pharmacological E2F inhibition mitigates experimental PH, supporting E2F1 as a therapeutic target in PAH. 1. This study identifies E2F1 as a previously unrecognized driver of PAH rather than only a downstream marker of cell-cycle activation.2. Genetic loss of E2f1 rescues hemodynamic and structural features of Egln1-driven PAH, and pharmacological E2F inhibition attenuates both Egln1-driven and monocrotaline-induced PH.3. Mechanistically, E2F1 links endothelial proliferation to Notch-associated arterial programming, AEC accumulation, and CAP1-to-iAEC-to-AEC trajectory progression. 1. E2F1 defines a tractable transcriptional node that integrates proliferative stress with arterial endothelial reprogramming, a core pathological feature of PAH vascular remodeling.2. Pan-E2F small-molecule inhibitors, several of which are in development for oncology, may be repurposable for PAH if E2F1-dependent endothelial arterial-programming signatures identify responsive disease states.3. Plasma- or tissue-based readouts of E2F1 activity may identify PAH patients most likely to benefit from E2F-directed therapy.

PMID 42465492
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