Panzem (2-methoxyestradiol)
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- LARVOL DELTA
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December 03, 2025
Mucinous cystic neoplasms of the pancreas demonstrate in situ production of estrogen.
(PubMed, Front Cell Dev Biol)
- "We identified that relative to histologically normal pancreas, and intraductal papillary mucinous neoplasm (IPMN), the stroma in MCN expresses significantly greater levels of estrone (E1), estradiol (E2), estriol (E3), 2-hydroxyestradiol (2-OHE2), 2-methoxyestrone (2-MeOE1), 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), at levels similar to those seen in the stroma in the normal ovary. These findings establish the functional capability of the ova rian-type stroma in MCN tumors for endogenous hormone production and show that the levels of estrogen in the stroma of MCN tumors approach those of the ovary. These findings serve as a basis for future studies examining the systemic effects of estrogen and the effects of estrogen on tumor progression, both in MCN tumors and tumor metastatic to the ovary."
Journal • CNS Tumor • Oncology • Pancreatic Cancer • Solid Tumor
December 03, 2025
Hypoxia-induced USP13 expression drives ferroptosis resistance and tumor immune evasion in hepatocellular carcinoma through the stabilization of ACLY.
(PubMed, Cell Death Discov)
- "A USP13 inhibitor, 2-Methoxyestradiol (2-Met), was used to evaluate its therapeutic efficacy...Pharmacological inhibition or knockdown of USP13 impedes HCC progression, induces ferroptosis, and enhances T cell-mediated cytotoxic effects. These results highlight that USP13 could be a promising therapeutic target for HCC."
Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD8 • HIF1A • USP13
September 04, 2025
2-Methoxyestradiol alleviates E. coli-induced endometritis in rats via inhibition of TLR-4/MyD88/NF-κB axis.
(PubMed, Eur J Pharmacol)
- "Finally, 2 ME significantly inhibited the expression of Toll-like receptor-4 (TLR-4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB). In conclusion, 2 ME inhibits E. coli-induced endometritis in rats via modulation of the TLR-4/MyD88/NF-κB axis."
IO biomarker • Journal • Preclinical • B Cell Lymphoma • Endometriosis • Infectious Disease • Infertility • Inflammation • Lymphoma • Oncology • Sexual Disorders • CCL2 • IL6 • MPO • MYD88 • TLR4 • TNFA
August 11, 2025
Transcriptional profiling uncovers microglial HIF-1α signaling as a therapeutic target of radiation-induced brain injury.
(PubMed, Free Radic Biol Med)
- "Pharmacological inhibition of HIF-1α with 2-methoxyestradiol led to partial recovery of cognitive function and selectively suppressed the expression of Ccl2, a key HIF-1α-associated chemokine implicated in neuroinflammatory signaling. These findings highlight the subtype-specific vulnerability of microglia to radiation and underscore the central role of HIF-1α-mediated transcriptional changes in RIBI. Targeting the microglial HIF-1α-Ccl2 axis may thus offer a promising strategy to mitigate late-onset cognitive dysfunction following cranial irradiation."
Journal • Brain Cancer • CNS Disorders • Cognitive Disorders • Oncology • Solid Tumor • Vascular Neurology • CCL2 • HIF1A
August 13, 2025
Estradiol Downregulates MicroRNA-193a to Mediate Its Anti-Mitogenic Actions on Human Coronary Artery Smooth Muscle Cell Growth.
(PubMed, Cells)
- "Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism...Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease."
Journal • Cardiovascular • Coronary Artery Disease • Eye Cancer • Oncology • Retinal Disorders • Solid Tumor • CCND1 • CDK4 • MIR193A • PCNA
August 20, 2025
2-Methoxyestradiol Treatment Prevents Graft-versus-Host Disease While Preserving Graft-versus-Leukemia Effect in Mice.
(PubMed, bioRxiv)
- "Furthermore, 2ME2 therapy is effective in preventing GVHD while preserving graft-versus leukemia (GVL) activity in mice. Our findings indicate that 2ME2 could be a novel and effective treatment for GVHD patients."
Journal • Preclinical • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Multiple Sclerosis • Oncology • Rheumatoid Arthritis • Rheumatology • CD4 • CD8 • IFNG • IL2
August 28, 2025
Ramulus Mori (Sangzhi) Alkaloids Improve Pancreatic β-Cell Function Through Gut Microbial and Intra-Islet 2-Methoxyestradiol Biosynthesis.
(PubMed, Biomedicines)
- "In vitro, 2-ME suppressed HIF-1α signaling and promoted insulin secretion, indicating that 2-ME may act as a crucial mediator of the beneficial effects of SZ-A. SZ-A improve β-cell function by increasing 2-ME levels via gut microbiota modulation and islet production, ultimately suppressing HIF-1α signaling and restoring β-cell homeostasis."
Journal • Diabetes • Type 2 Diabetes Mellitus • COMT • HIF1A
July 13, 2025
Development of an HPLC-FLD Method for Estradiol and Metabolites: Application of Solid-Phase Microextraction.
(PubMed, Int J Mol Sci)
- "Good linearity was observed for estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol (10-300 ng/mL; R2 = 0.9893-0.9995)...Solid-phase microextraction (SPME) offered advantages over liquid-liquid extraction. The method is suitable for quantifying estrogens in the 10 ng/mL-1 µg/mL range."
Journal
July 10, 2025
cJun-N-terminal kinase activity and mitosis perturbation drive the 2-methoxyestradiol-mediated enhancement of viral oncolysis by Epizootic Hemorrhagic Disease Virus-Tel Aviv University.
(PubMed, Sci Rep)
- "The findings suggest that combining OVs with MTAs, specifically EHDV-TAU and 2ME2, may exploit the enhanced susceptibility of cell-cycle-perturbed cancer cells to viral infection and cell death pathways. Such combinations may improve virus-based therapies for BC and potentially other cancers."
IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Hematological Disorders • Infectious Disease • Melanoma • Oncology • Solid Tumor • CALR • CDK1 • MAPK8
June 25, 2025
Redox-Responsive Dendritic Copolymer-Drug Conjugates Enhance Therapeutic Mitophagy Through Coordinated Microtubule Destabilization for Synergistic Triple-Negative Breast Cancer Therapy.
(PubMed, Acta Biomater)
- "Paclitaxel (PTX) and 2-methoxyestradiol (2ME) were conjugated to glutathione-stimuli responsive dendritic copolymers, resulting in DDS-PTX and DDS-2ME, respectively. Notably, the conjugates significantly reduced systemic toxicity compared to free drugs while maintaining hemocompatibility and organ safety. By integrating molecular-scale tumor microenvironment (TME) responsiveness with cytoskeletal-organelle crosstalk, this work establishes a mechanistically driven paradigm to amplify subcellular stress responses, offering a transformative strategy for refractory cancers with enhanced efficacy and safety."
Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer
June 14, 2025
Fucoxanthin Ameliorates Vascular Remodeling via Attenuating Oxidative Stress in Hypoxic Pulmonary Hypertension Rats.
(PubMed, J Nutr Biochem)
- "Notably, fucoxanthin exhibited effects similar to those of 2-methoxyestradiol (2ME2), an inhibitor of HIF-1α, on cell proliferation and ROS production in hypoxia-induced PASMCs...Collectively, fucoxanthin suppressed hypoxia-induced oxidative stress primarily by regulating the HIF-1α-ROS pathway, thereby alleviating pulmonary remodeling in HPH. Our findings represent a promising therapeutic strategy for HPH by improving pulmonary vascular remodeling."
Journal • Preclinical • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • HIF1A
May 24, 2025
Tea polyphenols and EGCG induce preeclampsia-like symptoms by reducing 2-methoxyestradiol.
(PubMed, J Steroid Biochem Mol Biol)
- "Furthermore, EGCG impaired the migration ability of HTR8/SVneo cells, which could be alleviated by 2-MeO-E2 supplementation. These findings indicate that tea polyphenols intake during pregnancy can cause PE-like symptoms by inhibiting COMT activity and production of 2-MeO-E2."
Journal • Cardiovascular • Gynecology • Hypertension • Renal Disease • COMT
May 22, 2025
2-Methoxyestradiol attenuates lung injury induced by chronic intermittent hypoxia via inhibiting the HIF1-α/SLC7A11 pathway.
(PubMed, Sci Rep)
- "The HIF-1α inhibitor, 2-ME2, effectively reverses CIH-induced lung tissue ferroptosis. The potential mechanism of 2-ME2 in inhibiting ferroptosis may involve suppressing the HIF-1α/SLC7A11 pathway."
Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • HIF1A • SLC7A11
May 06, 2025
2-Methoxyestradiol Inhibits the Oxygen-Sensing Pathway in Keloid Fibroblasts by Targeting HIF-1α/PHD.
(PubMed, Int Wound J)
- "In addition, the effects of 2-methoxyestradiol on the oxygen-sensing pathway in both hypoxic and normoxic keloid fibroblasts were evaluated. Our results suggest that 2-methoxyestradiol could be used to inhibit keloid fibroblast activity by inhibiting the oxygen-sensing pathway and its downstream effectors."
Journal • Fibrosis • Oncology • HIF1A • TNFA
April 28, 2025
Effects of an aryl hydrocarbon receptor ligand on human trophoblast cell development.
(PubMed, Hum Reprod)
- "The results suggest that AHR signaling activated by environmental pollutants could have a significant impact on placental development through mechanisms involving AHR activation. These findings may have broader implications for understanding how environmental factors affect fetal development."
Journal • CYP1A1 • CYP1B1
April 21, 2025
GLUT-Targeted Adhesive Nanoparticles Enhance the Oral Absorption and Anti-Tumor Effects of 2-Methoxyestradiol.
(PubMed, Int J Nanomedicine)
- "Compared with 2-ME-NPs, 2-ME-CMZ (1:1:9)-NPs significantly enhanced absorption through the mediation of multiple subtypes of GLUT, enhancing their original cellular uptake pathway and prolonging absorption time. These findings demonstrated that 2-ME-CMZ (1:1:9)-NPs are an extremely promising oral drug delivery system for 2-ME, and endowing GLUT-targeted drug-loaded nanoparticles with adhesion is an effective strategy for fully leveraging the role of GLUT in mediating oral absorption."
Journal • Oncology
March 27, 2025
Ubiquitin-specific protease 13 regulates FcεRI-mediated mast cell activation and allergic inflammation via SYK protein modulation.
(PubMed, Int J Biol Macromol)
- "Importantly, 2-methoxyestradiol (2-Meth) was identified as a potential inhibitor of USP13 and inhibited FcεRI-mediated MC activation effectively in vitro and in vivo. In conclusion, it elucidated the molecular mechanism by which USP13 regulated SYK stability in MCs. The USP13-SYK axis may serve as a therapeutic target for treating FcεRI-mediated activation of MCs and associated inflammatory responses."
Journal • Allergy • Inflammation • Targeted Protein Degradation • SYK • USP13
March 12, 2025
Estrogen metabolites and hydrogen peroxide - Missing elements in the pathophysiology and possible treatment of treatment-resistant depression?
(PubMed, Redox Biol)
- "In this study, we observed for the first time an association between unbalanced estrogen metabolism and elevated H202 levels in TRD patients. Reduced concentrations of 2-methoxyestradiol (2-ME2), 17α-estradiol (α-E2) and 17β-estradiol (β-E2) may be due to abnormal estrogen metabolism toward neurotoxic semiquinones and quinones which are a potential as yet undescribed mechanism responsible for generating oxidative stress (OS) in TRD."
Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry
March 12, 2025
Dynamic change of estrogen and progesterone metabolites in human urine during pregnancy.
(PubMed, Sci Rep)
- "We find that the levels of estrone, estradiol, estriol, 16-epiestriol, 17-epiestriol, 2-methoxyestradiol, and 4-hydroxyestrone gradually increase during pregnancy. The levels of progesterone, 20α-hydroxy progesterone, 5α-dihydroprogesterone and 5β-dihydroprogesterone first increase in the mid pregnancy and then decrease in the late pregnancy. In sum, this study comprehensively depicts the dynamic change of estrogen, progesterone, and their metabolites in human urine during pregnancy, which lays the foundation for hormone monitoring and early diagnosis of pregnancy complications, and further mechanistic study of the roles of these metabolites in pregnancy."
Journal
February 04, 2025
Central Interaction of 2-Methoxyestradiol and Lipoxygenase in AngII-Hypertension.
(PubMed, Hypertension)
- "These data suggest that 2-methoxyestradiol protects against AngII-induced hypertension and associated pathogenesis, most likely by inhibiting LOX/12(S)-HETE actions in the PVN of female mice. Therefore, the selective LOX inhibitors or 12(S)-HETE receptor antagonists could be useful in treating hypertension and its pathogenesis in postmenopausal, hypoestrogenic women or females with ovarian failure."
Journal • Cardiovascular • Hypertension • Inflammation • ALOX15 • LOX
January 30, 2025
Development of an accurate and sensitive assay for 2-methoxyestradiol using derivatization and liquid chromatography-tandem mass spectrometry.
(PubMed, Pract Lab Med)
- "The lower limit of quantification for 2ME was 2.5 pg/mL, indicating a satisfactory sensitivity. These findings demonstrated that this LC-MS/MS method combined with the MPDNP-F derivatization can provide accurate and highly sensitive quantification of 2ME."
Journal • Gynecology • Oncology
January 24, 2025
Combined Graphene Oxide with 2-Methoxyestradiol for Effective Anticancer Therapy in-vitro Model.
(PubMed, Int J Nanomedicine)
- "Graphene oxide flakes embroidered with 2-methoxyestradiol molecules may be a promising solution, bringing a new and important effect in the form of improving the bioavailability of the therapeutic substance, ie 2-ME. An appropriate dosage of GO-2-ME/rGO-2-ME, in which GO/rGO is a carrier of 2-methoxyestradiol (2-ME), can ensure effective penetration of the active substance through biological boundaries/membranes and controlled modification of cell signalling, ultimately leading to the selective elimination of malignant cells."
Journal • Preclinical • Melanoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • PTPN1
December 01, 2024
The role of HIF-1α/Bnip3/mitophagy in acrylonitrile-induced neuronal death in HT22 cells and mice: a potential neuroprotection target.
(PubMed, Chem Biol Interact)
- "Treatment with a HIF-1α activator, cobalt chloride (CoCl2), reversed these effects, while pretreatment with a HIF-1α inhibitor, 2-methoxyestradiol (2-MeOE2), augmented them...Furthermore, the HIF-1α/BNIP3 pathway was activated by the prolyl hydroxylase (PHD2) inhibitor, deferoxamine (DFO), which increased HT22 cell viability...In summary, under normal conditions, AN induced neurotoxicity by promoting PHD2-mediated HIF-1α degradation, disrupted the BNIP3-mediated mitophagy pathway, and enhanced apoptosis. Our findings underscore the effect of the HIF-1α/BNIP3-mediated mitochondrial autophagy in AN-induced neurotoxicity and suggest potential therapeutic strategies involving HIF-1α activation or BNIP3 overexpression for AN poisoning treatment."
IO biomarker • Journal • Preclinical • BCL2 • BECN1 • BNIP3 • HIF1A • MAP1LC3B
November 25, 2024
Synthesis of novel estradiol bisselenocyanate with unique 2-selenocyano-17-selenocyanoesteryl structure and evaluation of antitumor activity.
(PubMed, Mol Divers)
- "When compared to the positive control steroidal anti-tumor drug 2-methoxyestradiol, certain derivatives exhibited superior inhibitory activity against tumor cells in vitro, surpassing their monoselenocyanate precursors...Moreover, compound 4b exhibited significant inhibitory effects on cell migration and demonstrated remarkable inhibitory activity against HeLa xenograft tumors in zebrafish models. These findings suggest that these compounds hold potential as promising candidates for anti-tumor drugs and warrant further investigation."
Journal • Oncology
November 22, 2024
Differential bone morphology and hypoxia activity in skeletal metastases of ER+ and ER- breast cancer.
(PubMed, Commun Biol)
- "In the in vivo mouse model, the application of the hypoxia-inducible factor (HIF) inhibitor 2-methoxyestradiol demonstrates a promising efficacy in suppressing tumor growth and osteoclast differentiation in the bone lesions established by bone-tropic subpopulation of ER- MDA-MB-231 cell. Overall, our findings explore the complexity of phenotype and morphology in bone metastatic lesions of ER+ and ER- breast cancer, which offers a compelling rationale for leveraging HIF inhibitors to the treatment targeting skeletal complications of breast cancer bone metastases, especially for ER- tumors."
Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER
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