(1S,10R,11S,14S,15S)-4-methoxy-15-methyltetracyclo[8.7.0.02,7.011,15]heptadeca-2,4,6-triene-5,14-diol

• ChemBase ID: 72585
• Molecular Formular: C19H26O3
• Molecular Mass: 302.40794
• Monoisotopic Mass: 302.18819469
• SMILES: c1(c(cc2c(c1)[C@@H]1[C@@H](CC2)[C@H]2[C@](CC1)([C@H](CC2)O)C)O)OC
• Canonical SMILES: COc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2([C@H]1CC[C@@H]2O)C
• InChI: InChI=1S/C19H26O3/c1-19-8-7-12-13(15(19)5-6-18(19)21)4-3-11-9-16(20)17(22-2)10-14(11)12/h9-10,12-13,15,18,20-21H,3-8H2,1-2H3/t12-,13+,15-,18-,19-/m0/s1
• InChIKey: CQOQDQWUFQDJMK-SSTWWWIQSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,10R,11S,14S,15S)-4-methoxy-15-methyltetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-2,4,6-triene-5,14-diol; (1S,10R,11S,14S,15S)-4-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-triene-5,14-diol; (1S,10R,11S,14S,15S)-4-methoxy-15-methyltetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-2(7),3,5-triene-5,14-diol
• IUPAC Traditional name: 2-methoxyestradiol
• Synonyms: 1,3,5(10)-Estratriene-2,3,17β-triol 2-methyl ether; 2-Methoxy-estra-1,3,5(10)-triene-3,17β-diol; 1,3,5(10)-Estratriene-2,3,17-triol 2-methyl ether; 2,3,17β-Trihydroxy-1,3,5(10)-estratriene 2-methyl ether; 2-Hydroxyestradiol 2-methyl ether; 3,17β-Dihydroxy-2-methoxy-1,3,5(10)-estratriene; 2-Methoxyestradiol; 2-ME2; 2-Methoxyestradiol; (17β)-2-Methoxyestra-1,3,5(10)-triene-3,17-diol; 2-Methoxyestra-1,3,5(10)-triene-3,17β-diol; 2-Methoxyestradiol; NSC 659853; Panzem; 2-Methoxy 17β-Estradiol

Database IDs

• CAS Number: 362-07-2
• MDL Number: MFCD00010489
• Beilstein Number: 3147966
• PubChem SID: 24278561; 162037510
• PubChem CID: 66414

CALCULATED PROPERTIES

• Acid pKa: 10.290903
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 3.587823
• LogD (pH = 7.4): 3.5872755
• Log P: 3.58783
• Molar Refractivity: 86.3679 cm^3
• Polarizability: 33.824192 Å^3
• Polar Surface Area: 49.69 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: soluble10 mg/mL; ethanol: soluble10 mg/mL; H2O: insoluble; Methanol
• Apperance: Off-White Solid; white to faint yellow powder
• Melting Point: 188-190°C

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: KG7537500
• European Hazard Symbols: Nature polluting (N); Toxic (T)
• UN Number: 3077
• German water hazard class: 3
• Hazard Class: 9
• Packing Group: 3
• Risk Statements: 45-46-60-61-23/24/25-36/37/38-48; 45-46-60-61-23/24/25-36/37/38-48-51/53
• Safety Statements: 53-22-26-36/37/39-45; 53-22-26-36/37/39-45-61
• GHS Pictograms: GHS06; GHS08; GHS09
• GHS Signal Word: Danger
• GHS Hazard statements: H301 + H311 + H331-H315-H319-H335-H350-H360-H372-H410; H301-H311-H315-H319-H331-H335-H350-H360-H372
• GHS Precautionary statements: P201-P261-P273-P280-P301 + P310-P305 + P351 + P338; P201-P261-P280-P301 + P310-P305 + P351 + P338-P311
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 3077 9/PG 3
• Storage Temperature: -20°C

Pharmacology Properties

• Target: HIF
• Gene Information: human ... ESR1(2099), ESR2(2100)

Product Information

• Purity: ≥98.0% (HPLC)
• Grade: purum
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C19H26O3

DETAILS

Selleck Chemicals - S1233

Research Area

• Description: Pulmonary hypertension

Biological Activity

• Description: 2-Methoxyestradiol is an endogenous estrogen metabolite and naturally occurring mammalian tubulin polymerization inhibitor.
• In Vitro: 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. ^[1] 2-Methoxyestradiol inhibits proliferation of MCF-7 and BM cells with IC50 of 52 μM and 8 μM. ^[2] In MDA-MB-231 cells, 2-Methoxyestradiol inhibits HIF-1-mediated transcriptional activation of target genes without affecting the transcription of HIF-1α itself. ^[3] 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. ^[4]
• 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. ^[5]
• Clinical Trials: 2-Methoxyestradiol is currently in Phase II clinical trials in patients with plateau Phase or relapsed multiple myeloma. Combination treatment of 2-Methoxyestradiol and Bevacizumab is currently in Phase II clinical trials in patients with locally advanced or metastatic carcinoid tumors.

Combination Therapy

• Description: While the combination of 2-Methoxyestradiol and 4-Hydroxytamoxifen leads to the more potent inhibition of proliferation of MCF-7 and BM cells with IC50 of 6 μM and 4 μM, respectively. ^[2] In a AsPC-1 mouse model, the combination therapy of 2-Methoxyestradiol and gemcitabine leads to a significant reduction of average tumor volume by 83% compared to the non-treated group, while 2-Methoxyestradiol (2 mg) alone leads to a growth inhibition of 63% with no evident toxicity. ^[6]

Protocol

• Protocol: Kinase Assay ^[1]
• Microtubule depolymerizing activity: 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.
• Protocol: Cell Assay ^[1]
• Cell Lines: MDA-MB-435 and SK-OV-3
• Concentrations: 0-20 μM
• Incubation Time: 48 hours
• Methods: 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.
• Protocol: Animal Study ^[5]
• Animal Models: 9L-V6R cells are injected into the brains of Fischer 344 rats
• Formulation: 2-Methoxyestradiol is dissolved in DMSO.
• Doses: ≤600 mg/kg
• Administration: Administered via i.p.

References

• References: [1] Rao PN, et al. Steroids. 2002, 67(13-14), 1079-1089.
• References: [2] Seeger H, et al. J Steroid Biochem Mol Biol. 2003, 84(2-3), 255-257.
• References: [3] Mabjeesh NJ, et al. Cancer Cell. 2003, 3(4), 363-375.
• References: [4] Salama SA, et al. Fertil Steril. 2012.
• References: [5] Kang SH, et al. Cancer Res. 2006, 66(24),11991-11997.
• References: [6] Fotopoulou C, et al. Anticancer Res. 2010, 30(11), 4619-4624.

Sigma Aldrich - M6383

Biochem/physiol Actions
2-Methoxyestradiol (2-ME) is a potent inhibitor of endothelial cell proliferation and angiogenesis. A major estradiol metabolite, it has little affinity for classical estrogen receptors.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. M6383.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - M262625

2-Methoxy 17β-Estradiol is a natural metabolite of 17β-Estradiol which is devoid of estrogenic activity. Inhibits cell proliferation and angiogenesis. 2-Methoxy 17β-Estradiol binds to the colchicine binding site of tubulin, and has been suggested to func

REFERENCES

• Rao PN, et al. Steroids. 2002, 67(13-14), 1079-1089.
• Seeger H, et al. J Steroid Biochem Mol Biol. 2003, 84(2-3), 255-257.
• Mabjeesh NJ, et al. Cancer Cell. 2003, 3(4), 363-375.
• Salama SA, et al. Fertil Steril. 2012.
• Kang SH, et al. Cancer Res. 2006, 66(24),11991-11997.
• Fotopoulou C, et al. Anticancer Res. 2010, 30(11), 4619-4624.
• Cushman, M., et al.: J. Med. Chem., 38, 2041 (1995)
• D’Amato, R.J., et al.: Proc. Natl. Acad. Sci. USA, 91, 3964 (1995)
• Forsis, T., et al.: Nature, 368, 237 (1994)