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tamoxifen (tamoxifen, Douglas)

✓ Approved

Douglas Pharmaceuticals Limited · ESR1 · 小分子

什么是 tamoxifen？

tamoxifen 是一种小分子，由Douglas Pharmaceuticals Limited研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名tamoxifen, Douglas
公司Douglas Pharmaceuticals Limited
药物类别小分子
分子靶点ESR1
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Douglas Pharmaceuticals Limited

作用机制

分子靶点

tamoxifen 作用于 1 个分子靶点：

ESR1estrogen receptor 1 (ER, ESR)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

tamoxifen 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancer✓ Approved

相关研究文献

PubMedACS omega2026-10-25

Use of Tamoxifen Derivatives in Combination with Colistin against Colistin-Resistant Acinetobacter baumannii.

Panadero Irene Molina IM, Rey Hidalgo Angela A, Rimoldi Isabella I, Facchetti Giorgio G et al.

Drug repurposing has led to the identification of tamoxifen, a well-known chemotherapy drug, as a compound with relevant antibacterial properties. In this field, the development of new tamoxifen derivatives with antimicrobial activity, particularly against colistin-resistant Acinetobacter baumannii, represents an important area of research. We evaluated the MICs of 22 and 3 tamoxifen derivatives against wild-type and colistin-resistant A. baumannii strains, respectively, using microdilution assays, either as monotherapy or in combination with colistin. While all derivatives showed MIC values above 64 mg/L when tested as monotherapy, combining derivatives 1, 14, and 18 with colistin reduced tamoxifen derivatives' MICs to 0.125-2 mg/L for the reference strain ATCC 17978 and to 0.5-1 mg/L for the colistin-resistant Ab22 strain. Growth assays showed that these derivatives delayed Ab22 proliferation during the first 4 h. Moreover, these derivatives increased membrane permeabilization without altering the expression of the outer membrane proteins (OMPs). These findings suggest that tamoxifen derivatives in combination with colistin exhibit antibacterial activity against a colistin-resistant A. baumannii, potentially broadening the spectrum of available drug treatments for combating MDR A. baumannii.

PMID 42923980
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PubMedBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2026-10-25

Estrogen receptor modulation by a newly-identified cannabinoid in a preclinical model of breast cancer.

Cohen Vered V, Besser Elazar E, Shotan Stav Roni SR, Procaccia Shiri S et al.

Breast cancer is a diverse group of diseases comprising subtypes with distinct behavior and response to therapy. Tumors that express estrogen receptor alpha (ERα) and depend on estrogen constitute ∼65% of all breast cancer cases. Common endocrine therapy for this kind of breast cancer includes Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen. However, despite the clear benefits, many patients do not complete the recommended 5 and sometimes 10 years of treatment because of adverse effects. Medical cannabis is increasingly used by cancer patients, primarily for palliative care, yet its direct antitumor potential in breast cancer remains poorly understood. Examine whether cannabis-derived compounds exert selective antitumor effects in breast cancer and elucidate the underlying molecular mechanisms. A combination of in vitro experiments in multiple ER-positive breast cancer cell lines with in vivo validation in an estrogen-dependent xenograft mouse model. Breast cancer cell lines representing different molecular subtypes were evaluated. A panel of chemically distinct cannabis extracts was initially screened for cytotoxic activity and subsequently tested in combination with SERMs. Extracts were chemically profiled using ESI-LC/MS. Phytocannabinoid fractionation, chemical analyses, and structural elucidation were performed to isolate and characterize the bioactive phytocannabinoid in the only cannabis extract identified in the initial screen as effective in combination with tamoxifen. The mechanism of action of this phytocannabinoid was investigated in vitro using molecular and biochemical assays. Finally, antitumor efficacy was assessed in vivo using an estrogen-dependent ER-positive breast cancer xenograft mouse model. We found a unique cannabis extract, CANN14, capable of sensitizing ER-positive breast cancer cells to the cytotoxic effect of tamoxifen. We identified a novel phytocannabinoid 373.15b that mimicked the effect of the whole extract without any toxicity by itself. It has a unique structure of a dihydroxyphenol with an acetate group attached to the aromatic ring, distinguishing it from known cannabinoid scaffolds. Cannabinoid 373.15b modulated estrogen signaling by decreasing the mRNA and protein expression levels of ERα, as well as its transcriptional activity, possibly through a signaling pathway involving RASSF1A and Hippo signaling components. In an in vivo mouse model, treatment with 373.15b reduced tumor volume and weight, with a more profound effect when combined with tamoxifen. The work presented here identifies a novel cannabinoid that modulates ERα signaling and enhances the antitumor efficacy of SERMs. The findings suggests that co-therapy of 373.15b with SERMs may allow dose reduction of conventional therapy, and by that, diminish the associated adverse effects and improve patient quality of life. The newly identified cannabinoid 373.15b reduces ERα expression and activity through RASSF1A and Hippo signaling pathway thus exerting antitumor effects.

PMID 42927724
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PubMedBiology of reproduction2026-10-25

Genetic engineering in the Post Implantation Uterus using a 4-hydorxytamofen Regulated Cre Recombination.

Li Shuyun S, DeMayo Francesco J FJ

The tamoxifen-inducible PgriCreERT2 mouse model enables temporal Cre recombination in progesterone receptor (Pgr)-expressing reproductive tissues. However, it remains unclear whether the PgriCreERT2 model can be safely activated during pregnancy, as tamoxifen exposure in pregnant mice can adversely affect pregnancy outcomes. Here, we established a 4-hydroxytamoxifen (4-OHT) dosing strategy for inducing Cre recombination after implantation using the PgriCreERT2 model. Pregnant females carrying PgriCreERT2 and a Cre-dependent Rosa26Sun1 reporter were administered a single dose of 4-OHT at gestational day (GD) 8.5. Dose-dependent effects on pregnancy and reporter recombination were evaluated using gross morphology, immunofluorescence, histology, placental and fetal measurements, gestation length, litter size, and resorption rate. A dose of 37.5 mg/kg produced robust SUN1 reporter activation in post-implantation uterine tissues while avoiding the overt adverse effects observed at the higher dose tested. Reporter-positive cells were detected predominantly in the uterus. Placental morphology, steroid hormone receptor (PGR and estrogen receptor alpha (ERα/ESR1)), placental development, and vascularization were preserved following treatment. These findings establish a practical 4-OHT induction regimen for temporally controlled recombination in the PgriCreERT2 model during post-implantation pregnancy and provide a methodological framework for studying uterine cell function during decidualization, placentation, and maternal-fetal development while reducing pregnancy-related confounding effects.

PMID 42921811
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PubMedbioRxiv : the preprint server for biology2026-10-25

Cardiomyocyte Perm1 sustains cardiac bioenergetic reserve and exercise capacity.

Tachibana Shizuko S, Le Tina T, Schenk Simon S, Feng Wei W et al.

The PGC-1/ERR axis controls both steady-state mitochondrial respiration and the capacity to expand ATP production on demand, but whether this reserve function requires dedicated downstream effectors, and whether its loss is detectable at rest, remain unclear. We tested whether Perm1, a striated muscle-specific PGC-1/ERR-induced regulator, is required for cardiac bioenergetic reserve. We generated cardiomyocyte-specific Perm1 knockout mice using constitutive αMHC-nCre and tamoxifen-inducible αMHC-MerCreMer drivers and followed to 12 months and to 4 months after tamoxifen, respectively. Mitochondrial respiration was measured by high-resolution respirometry and ultrastructure by electron microscopy; energetic capacity under load was tested by treadmill exercise with tissue ATP quantification and by β-adrenergic stimulation of neonatal cardiomyocytes. Perm1 deletion did not perturb cardiac development; neither constitutive nor adult-onset deletion impaired cardiac structure and systolic function through 12 months. Despite this, mitochondrial respiration was reduced by 20-25% without a change in total mitochondrial content or OxPhos subunit abundance. MICOS components MIC60 and MIC19 were selectively reduced, and mitochondria redistributed from subsarcolemmal to interfibrillar compartments. Perm1-deficient mice of both sexes showed ∼50% lower treadmill endurance at 6 and 12 months and failed to maintain cardiac ATP at a submaximal workload, whereas gastrocnemius ATP and plasma lactate were unaffected. β-Adrenergic stimulation raised ATP content in control cardiomyocytes, and Perm1 knockdown blunted this response. Perm1 is a cardiomyocyte-intrinsic determinant of cardiac bioenergetic reserve: dispensable for resting function but required to expand ATP production when demand rises. This regulation is invisible to resting phenotyping and emerges only under stress.

PMID 42926467
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PubMedScience bulletin2026-10-25

Modular synthesis of unsymmetrical all-carbon tetrasubstituted alkenes via Pd-catalyzed multi-component coupling.

Yu Yajun Y, Chen Kai K, Zhu Qi Q, Ma Xingxing X et al.

Tetrasubstituted alkenes constitute privileged architectures in material science, biomedicine, and chemistry. However, achieving their stereocontrolled synthesis-especially for molecules with four distinct substituents-remains a formidable challenge, as conventional methods lack the necessary modularity and stereoselectivity. Herein, we report a palladium-catalyzed three-component cascade reaction that directly couples alkynyl tetracoordinate boron compounds with two different aryl halides in a single vessel. The reaction proceeds through initial coupling with one aryl halide to form an alkenylboron intermediate, followed by a second Suzuki-type coupling with the other aryl halide. This strategy effectively addresses long-standing challenges of chemoselectivity and byproduct formation in the synthesis of tetrasubstituted alkenes. It enables the modular assembly of unsymmetrical tetrasubstituted alkenes with precise control over chemo-, regio-, and stereoselectivity. Notably, this method provides access even to the most challenging targets bearing four distinct substituents in a stereodefined manner. The reaction proceeds under mild conditions, exhibits exceptional functional group tolerance, and accommodates a broad substrate scope (>100 examples). Significantly, several derivatives exhibit aggregation-induced emission (AIE) with a distinct bathochromic shift (red-shift) in the solid state, underscoring the potential of this unique alkene architecture for developing solid-state red-emitters. Furthermore, we demonstrate the concise synthesis of the pharmaceutical agents Toremifene and Tamoxifen using this method. This work establishes a versatile and practical platform for accessing these coveted architectures, with broad implications for synthetic chemistry and materials science.

PMID 42926179
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PubMedbioRxiv : the preprint server for biology2026-10-25

VITAL-3D: Volumetric Single-Cell Quantification Reveals Microenvironment-Dependent Drug Responses in Breast Cancer.

Jin Chongguang C, Chu Tiffany T, Zhang Qiming Q, Wirtz Denis D et al.

Preclinical drug evaluation relies heavily on two-dimensional (2D) monolayer assays, which fail to recapitulate the structural and functional complexity of the tumor microenvironment and may therefore misrepresent therapeutic efficacy. Here, we present VITAL (Volumetric Imaging-based Toxicity and Live Analysis), a high-throughput imaging platform that enables direct single-cell quantification of proliferation and cell death in both 2D and three-dimensional (3D) extracellular matrix (ECM) cultures using a 96-well format. By combining volumetric imaging with automated single-cell analysis, VITAL enables dynamic assessment of drug responses beyond conventional viability assays and EC₅₀ measurements. Using breast cancer cell lines treated with anticancer agents, we systematically compared drug responses between 2D and 3D microenvironments. Although EC₅₀ values were often comparable between culture formats, growth kinetics and concentrations required to induce complete growth arrest or net cell loss differed substantially in 3D cultures. In particular, drug concentrations required to induce net cell loss were consistently higher in 3D, revealing microenvironment-dependent survival responses that were not captured by EC₅₀ alone. Furthermore, clinically expected subtype-specific responses, including tamoxifen sensitivity in ER-positive cells and olaparib sensitivity in BRCA1-mutant cells, were more accurately resolved under 3D culture conditions and extended treatment durations. Together, these findings demonstrate that growth-based, single-cell quantification provides a more comprehensive assessment of therapeutic efficacy than conventional endpoint measurements and establish VITAL as a scalable platform for physiologically relevant preclinical drug screening.

PMID 42922656
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