Molecular Weight (MW)

302.41

Formula

C19H26O3

CAS No.

362-07-2

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 60 mg/mL (198.4 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

2% DMSO+corn oil: 5mg/mL

Synonyms

NSC 659853; NSC-659853; NSC659853; 2-ME; 2-Methoxy Estradiol. 2-methoxyestradiol; US brand name: Panzem. Abbreviation: 2-ME2.

Chemical Name: (8R,9S,13S,14S,17S)-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol

SMILES Code: OC1=C(OC)C=C2[C@@]3([H])CC[C@]4(C)[C@@H](O)CC[C@@]4([H])[C@]3([H])CCC2=C1

In Vitro

In vitro activity: 2-Methoxyestradiol exhibits the inhibitory activity of cellular proliferation in a breast carcinoma cell line MDA-MB-435 and an ovarian carcinoma cell line SK-OV-3 with IC50 of 1.38 μM and 1.79 μM, respectively. Furthermore, 2-Methoxyestradiol also inhibits cellular microtubule depolymerization in rat aortic smooth muscle A-10 cells with EC50 of 7.5 μM. 2-Methoxyestradiol inhibits proliferation of MCF-7 and BM cells with IC50 of 52 μM and 8 μM. In MDA-MB-231 cells, 2-Methoxyestradiol inhibits HIF-1-mediated transcriptional activation of target genes without affecting the transcription of HIF-1α itself. A recent study shows that 2-Methoxyestradiol (0.5 μM), blocks TGF-β3-induced expression of collagen (Col) type I(αI), Col III(αI), plasminogen activator inhibitor (PAI) 1, connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA). Moreover, 2-Methoxyestradiol ameliorates TGF-β3-induced Smad2/3 phosphorylation and nuclear translocation, and inhibits TGF-β3-induced activation of the PI3K/Akt/mTOR pathway

Kinase Assay: The effects of 2-Methoxyestradiol on cellular microtubule depolymerization are determined by indirect immunofluorescence techniques in rat aortic smooth muscle A-10 cells. Microtubules are visualized using a β-tubulin antibody. Three viewers determines the percent microtubule loss for each treatment concentration. The data are averaged and plotted as percent microtubule loss versus drug concentration and the EC50s for microtubule depolymerization calculated from the log dose–response curves.

Cell Assay: The sulforhodamine B (SRB) assay is used to evaluate the antiproliferative activity of 2-Methoxyestradiol in the MDA-MB-435 and SK-OV-3 cell lines. Cells a plated into 96-well plates and allowed to grow and attach for 24 hours followed by addition of 2-Methoxyestradiol or vehicle controls. The cells are incubated with drugs for 48 hours and then the cellular protein is fixed, stained, and concentration determined by absorbance at 560 nm. Log dose–response curves are constructed for each experiment and the IC50 for inhibition of proliferation determined.

In Vivo

In a 9L rat glioma (9L-V6R) rat model, 2-Methoxyestradiol significantly decreases HIF-1 activity and inhibits the tumor growth in a dose-dependent manner by 4-fold reduction for 60 mg/kg/day, and 23-fold reduction for 600 mg/kg/day, respectively.

Animal model

9L-V6R cells are injected into the brains of Fischer 344 rats

Formulation & Dosage

Dissolved in DMSO;<600mg/kg; i.p. injection

References

Steroids. 2002 Dec;67(13-14):1079-89; Carcinogenesis. 2000 Apr;21(4):735-40; Cancer Res. 2006 Dec 15;66(24):11991-7.