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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
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Accessible (Haz class 3, 4, 5 or 8), International
The response of mammalian cells to hypoxia is mediated by a family of transcription factors known as HIF (hypoxia-inducible factors). The subunits of HIF, HIF-1α and HIF-2α are structurally similar and can be degraded rapidly under normoxia. 2-Methoxyestradiol can inhibit HIF-1α and HIF-2α expression, as well as depolymerize microtubules. Treatment with 2-Methoxyestradiol (5 - 100 μM) for 16h can reduce expression of HIF-1α dose-dependently in PC-3 and MDA-MB-231 cells, accompanied with the reduced activity of HIF-1 and the expression of its target protein, VEGF, and without effect on HIF-1α mRNA levels or rate of protein degradation. Treatment with 2-Methoxyestradiol (10 - 100 μM) overnight can depolymerize microtubules and impair nuclear accumulation of HIF-1α in PC-3 cells under hypoxia. Daily oral administration of 2-Methoxyestradiol, 150 mg/kg, for 33 days suppressed tumor growth and angiogenesis, as well as depolymerized microtubules in breast cancer orthotopic models. The inhibition of HIF-2α expression and microtubule-depolymerization by 2-Methoxyestradiol can also be observed in endothelial cells[1].
作用机制
2-Methoxyestradiol inhibits the expression, nuclear accumulation and transcriptional activity of HIF-1α[1]. However, the accurate mechanism of action is unknown now.
2-Methoxyestradiol/2-甲氧基雌二醇 细胞实验
Cell Line
Concentration
Treated Time
Description
References
metastatic osteosarcoma 143B cells
1 nM
8 h
To compare the effects of physiological (1 nM) and pharmacological (1 μM) concentrations of 2-ME on•NO2 generation, results showed significant increase in•NO2 levels even at physiological concentration.
Redox Biol. 2020 May;32:101522.
metastatic osteosarcoma 143B cells
1 μM
2 h
To investigate the effect of 2-ME on the generation of reactive nitrogen species (RNS) in 143B cells, results showed peak NO release at 2 h and peak ONOO− release at 8 h post-treatment.
Redox Biol. 2020 May;32:101522.
primary cortical cultures (PCCs)
10 μM
16 h
inhibited HIF-1α activation and nuclear translocation, preventing hypoxia-mediated STI-1 production
EMBO Mol Med. 2013 Aug;5(8):1227-46.
A549 cells (3D spheroid model)
0.78 μM–200 μM
48 h
To evaluate the effect of 2-methoxyestradiol on the viability of 3D spheroid A549 cells, results showed that 2-methoxyestradiol significantly reduced the viability of 3D spheroid A549 cells in a dose-dependent manner.
Redox Biol. 2022 Sep;55:102395.
A549 cells(2D spheroid model)
0.78 μM–100 μM
24 h
To evaluate the effect of 2-methoxyestradiol on the viability of A549 cells, results showed that 2-methoxyestradiol significantly reduced the viability of A549 cells in a dose-dependent manner.
Redox Biol. 2022 Sep;55:102395.
LNCaP cells
3µM
2 h
2-ME 2 significantly reduced FLIP expression.
Clin Cancer Res. 2009 Mar 1;15(5):1601-11.
PC-3 cells
3µM
2 h
2-ME 2 reduced the levels and promoter activity of FLIP (p=0.001), decreased FLIP binding to Fas or FADD, increased cleavage of caspase-8 and Bid, and induced apoptosis.
Clin Cancer Res. 2009 Mar 1;15(5):1601-11.
SH-SY5Y cells
1, 2.5, 4, 5 μM
48 or 72 h, or 1 to 8 days
2-ME significantly inhibited the proliferation of SH-SY5Y cells and induced apoptosis.
Cancer Lett. 2011 Dec 27;313(2):201-10.
SK-N-SH cells
1, 2.5, 4, 5 μM
48 or 72 h, or 1 to 8 days
2-ME significantly inhibited the proliferation of SK-N-SH cells and induced apoptosis. DNA fragmentation and chromatin condensation were observed in the cells treated with 4 μM 2-ME for 72 h.
Cancer Lett. 2011 Dec 27;313(2):201-10.
2-Methoxyestradiol/2-甲氧基雌二醇 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 J male mice
Osteoporosis model
Gavage
75 mg/kg
Once daily for 4 weeks
To study the improvement of bone-vessel metabolism in aged mice and the damage in young mice by 2-Methoxyestradiol
Stem Cell Res Ther. 2022 Feb 5;13(1):59
Mice
Lumbar spine instability (LSI) surgery model
Intraperitoneal injection
75 mg/kg
Once daily for 2 or 4 weeks
Evaluated the therapeutic effect of 2ME2 on experimental intervertebral disc degeneration, showing that 2ME2 significantly attenuated LSI surgery-induced disc degeneration, reduced HIF1α expression, and decreased EP cartilage ossification
Bone Res. 2022 Jan 5;10(1):2
Wistar rats
Cyclosporine A-induced nephrotoxicity model
Oral
5 mg/kg
Once daily for three weeks
To evaluate the protective effects of 2ME-TPGS micelles against cyclosporine A-induced nephrotoxicity. Results showed that 2ME-TPGS significantly ameliorated the deterioration of renal function markers, attenuated pathological changes in kidney tissues, and exhibited significant anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic effects.
2-ME 2 intervention led to tumor regression in 90% of the animals, significantly reduced prostate seminal vesicle complex (PSVC) weight (p<0.001), and significantly lowered pathological scores (p<0.001). Tumor regression was associated with reduced expression of FLIP and Sp1.
Clin Cancer Res. 2009 Mar 1;15(5):1601-11.
Mice
Cyp1b1−/− and Cyp1b1+/+ mice
Intraperitoneal injection
1.5 mg/kg
Every 3rd day for 14 days
2-Methoxyestradiol reduced angiotensin II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria, and attenuated end-organ damage.
Hypertension. 2017 Jun;69(6):1104-1112
Female mice
CPLA2α+/+/Cyp1b1+/+, cPLA2α−/−/Cyp1b1+/+, and cPLA2α+/+/Cyp1b1−/−
Intraperitoneal injection
1.5 mg/kg
Every third day for 14 days
2-Methoxyestradiol ameliorates Ang II-induced hypertension, renal fibrosis, and reactive oxygen species production by inhibiting cPLA2α activity and reducing prostaglandin E2 and thromboxane A2 production.
Hypertension. 2021 Nov;78(5):1368-1381
2-Methoxyestradiol/2-甲氧基雌二醇 动物研究
Dose
Rat: min = 0.1 mg/kg, max = 75 mg/kg[2] (p.o.); min = 60 mg/kg, max = 600 mg/kg[3] (i.p.)
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