Metabolism / Metabolites
Known metabolites of 2-methoxyestrone include (8R,9S,13S,14S)-2-methoxy-13-methyl-3-[(2R,3R,4S,5S,6S)-3,4,5,6-tetrahydroxyoxacyclohexane-2-yl]oxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17-one. 2-Methoxyestrone is a known metabolite of 2-hydroxyestrone.

[1]. pKa values of estrone, 17 beta-estradiol and 2-methoxyestrone. Steroids. 1979 Nov;34(5):485-99.

2-Methoxyestrone is a 17-oxosteroid, a product of estrone with a methoxy group replacing the hydrogen at the 2-position. It is a metabolite in both humans and mice. It is a 3-hydroxysteroid, 17-oxosteroid, alicyclic ketone, phenolic compound, aromatic ether, and phenolic steroid. Functionally, it is related to estrone. 2-Methoxyestrone is a metabolite found in or produced by Escherichia coli (K12 strain, MG1655 strain). Data on its presence in humans has been reported. 2-Methoxyestrone is a metabolite formed during the methylation of 2-hydroxyestrone (2-OHE1) by catechol-O-methyltransferase (COMT), possessing potential anticancer activity and very weak estrogenic activity. The mechanism of the antitumor activity of 2-methoxyestrone (2-OMeE1) is still unclear. A higher 2-methoxyestrone (2-OMeE1)/2-OHE1 ratio indicates higher methylation efficiency and is associated with a lower cancer risk.

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1. Chemical background of 2-methoxyestrone:
-2-methoxyestrone is a methylated derivative of estrone (a natural estrogen); its chemical structure differs from estrone in that it has a methoxy group (-OCH₃) at the C-2 position of ring A[1]
-It is a steroid compound with low water solubility but is soluble in polar organic solvents (such as ethanol and methanol), which is crucial for the determination of its pKa value[1]
2. pKa value determination results:
-The pKa value of 2-methoxyestrone was determined by potentiometric titration in a 50% (v/v) ethanol-water mixture (a commonly used solvent system for steroid pKa analysis)[1]
-2-methoxyestrone has a dissociable phenolic hydroxyl group (on ring A); its pKa value was determined to be 10.3 ± 0.1[1]
- Comparison with related estrogens: In the same solvent system, the pKa value of 2-methoxyestrone was higher than that of estrone (pKa = 10.0 ± 0.1) and 17β-estradiol (pKa = 10.2 ± 0.1), indicating that C-2 methoxy increases the acidity of the phenolic hydroxyl group [1] 3. pKa determination experimental steps: - Solvent preparation: Prepare a 50% (v/v) ethanol-water mixture using anhydrous ethanol and deionized water; degas the mixture with nitrogen to avoid interference from CO₂ [1] - Sample preparation: Dissolve 2-methoxyestrone in a 50% ethanol-water mixture to a final concentration of 0.001 M; stir the solution until completely dissolved [1] - Potentiometric titration: Use 0.1 M standard sodium hydroxide (NaOH) solution as the titrant; titrate at 25 ± The titration was performed at 0.5°C (constant temperature) [1] - Data acquisition: After each addition of NaOH (0.05 ml increment), the pH value of the 2-methoxyestrone solution was continuously recorded using a calibrated pH electrode; a titration curve (the relationship between pH and the volume of NaOH added) was plotted [1] - pKa calculation: The pKa value was obtained from the inflection point of the titration curve (at which point the concentration of the protonated form was equal to the concentration of the deprotonated form of 2-methoxyestrone). Each measurement was repeated 3 times to ensure accuracy, and the relative standard deviation (RSD) was <1% [1] 4. Significance of pKa determination: - The pKa value of 2-methoxyestrone is a key physicochemical parameter that affects its solubility, ionization state and partition behavior in biological systems (e.g., between aqueous and lipid phases); this data provides a basis for future studies on its biological fate (e.g., absorption, distribution) [1]

C19H24O3

300.39206

300.172

362-08-3

2-Methoxyestrone-d4;949885-90-9;2-Methoxyestrone-13C,d3;1217460-84-8;2-Methoxyestrone-13C6

440624

White to off-white solid powder

1.2±0.1 g/cm3

463.5±45.0 °C at 760 mmHg

187.0 - 189.5 °C

165.9±22.2 °C

0.0±1.2 mmHg at 25°C

1.576

3.39

1

3

1

22

462

4

C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CCC4=CC(=C(C=C34)OC)O

WHEUWNKSCXYKBU-QPWUGHHJSA-N

InChI=1S/C19H24O3/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/h9-10,12-13,15,20H,3-8H2,1-2H3/t12-,13+,15-,19-/m0/s1

(8R,9S,13S,14S)-3-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~166.45 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)