2-methoxyestradiol (2-ME2), an endogenous metabolite of 17β -estradiol (E2) with oral activity, is an apoptosis inducer and angiogenesis inhibitor with effective antitumor activity. Methoxyestradiol can also destabilize microtubules. Methoxyestradiol is a potent inhibitor of superoxide dismutase (SOD) and reactive oxygen species (ROS) that can induce autophagy in transformed cell line HEK293, cancer cell line U87 and HeLa.
Sci Rep. 2016 Jul 1;6:28612.
Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases.
2-Methoxyestradiol purchased from AbMole
_figure5_2-methoxyestradiol(2-me).jpg) |
Source | Sci Rep (2016). Figure 5. 2-methoxyestradiol (2-ME) was purchased from Abmole |
| Method | CHIP assay and Immunohistochemistry staining | |
| Cell Lines | in vivo experiment | |
| Concentrations | 25mg/kg daily | |
| Incubation Time | 30 days | |
| Results | Administration of 2-ME and digoxin significantly decreased AngII- mediated HIF-1α, VEGF, MMP-2 and MMP-9 overexpression in the homogenates of the whole aortas, as shown in Fig. 5A. 2-ME and digoxin decreased the AngII induced HIF-1α levels accumulation and elastin degradation in the aorta (Fig. 5B). |
_figure4_2-methoxyestradiol(2-me).jpg) |
Source | Sci Rep (2016). Figure 4. 2-methoxyestradiol (2-ME) was purchased from Abmole |
| Method | in vivo experiment | |
| Cell Lines | ||
| Concentrations | 25mg/kg daily | |
| Incubation Time | 30 days | |
| Results | Both non-selective HIF-1α inhibitors 2-ME (25 mg/kg/day, s.c.) and digoxin (1.25 mg/kg/day, i.p.) significantly improved the survival rates (log rank test, n= 20 in each group, p < 0.05, Fig. 4B); decreased the incidences of AAA (0% vs. 84% vs. 35%, vs. 40%, p < 0.01, Fig. 4C), the severities of AAA, in terms of less type III and type IV lesions (43% vs. 15%, vs. 15%, p < 0.05, Fig. 4D) and the external diameters of the aorta (0.67 ± 0.11 mm vs. 1.68.± 0.77 vs. 0.96± 0.30 vs. 1.10± 0.53 mm, p< 0.05, Fig. 4E). |
_figure3_2-methoxyestradiol(2-me).jpg) |
Source | Sci Rep (2016). Figure 3. 2-methoxyestradiol (2-ME) was purchased from Abmole |
| Method | CHIP assay | |
| Cell Lines | HAECs | |
| Concentrations | 6 μM | |
| Incubation Time | 30 min | |
| Results | We found that both 2-ME and digoxin attenuated AngII and oxPAPC induced up-regulation of MMP-2 and MMP-9 (n = 5, Fig. 3) |
| Cell Experiment | |
|---|---|
| Cell lines | MCF-7 and MDA-MB-231 cells |
| Preparation method | Cell culture and cell treatment. MCF-7 estrogen receptor-positive (ER+ve) human breast cancer cells, MDA-MB-231 ER-negative (ER−ve) human breast cancer cells were obtained from the American Type Culture Collection (LGC Promochem, Teddington, UK). Cells were routinely cultured in RPMI-1640 medium supplemented with 10% (v/v) fetal calf serum, 1% L-glutamine (200 mM), 1% non-essential amino acids (100 ×) and 1% bicarbonate (7.5%) from Sigma and maintained in a humidified incubator under 5% CO2 atmosphere at 37°C. For experiments using hypoxic conditions, cells were incubated under 1% O2 and 5% CO2 atmosphere at 37°C. |
| Concentrations | 0.5 μM |
| Incubation time | 18 h |
| Animal Experiment | |
|---|---|
| Animal models | mice bearing MCF-7 and MDA-MB-231 xenografts model |
| Formulation | 10% tetrahydrofuran: 90% propylene glycol |
| Dosages | 40 or 75 mg/kg |
| Administration | orally daily for 28 days |
| Molecular Weight | 302.41 |
| Formula | C19H26O3 |
| CAS Number | 362-07-2 |
| Solubility (25°C) | DMSO ≥ 60 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[3] Lakhani NJ, et al. Pharmacotherapy. 2-Methoxyestradiol, a promising anticancer agent.
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| HIV-IN-7
Axl-IN-16 is a Axl inhibitor. |
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HIF-2α-IN-9 is an inhibitor ofHIF-2α. |
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PHD-IN-2 is a PHD antagonist (IC50: < 5 nM). |
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