You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:02:38 UTC
HMDB IDHMDB00405
Secondary Accession NumbersNone
Metabolite Identification
Common Name2-Methoxyestradiol
Description2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It is derived from estrogen, although it binds poorly to known estrogen receptors, and belongs to the family of drugs called angiogenesis inhibitors. It has undergone Phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. The CAS name for 2ME2 is (17 beta)-2-methoxyestra-1,3,5(10)-triene-3,17-diol. It also acts as a vasodilator.
Structure
Thumb
Synonyms
ValueSource
1,3,5(10)-ESTRATRIEN-2,3,17-BETA-triol 2-methyl etherChEBI
2-Hydroxyestradol 2-methyl etherChEBI
2-MethoxyestradiolChEBI
2-Methoxyestradiol-17betaChEBI
PanzemChEBI
1,3,5(10)-ESTRATRIEN-2,3,17-b-triol 2-methyl etherGenerator
1,3,5(10)-ESTRATRIEN-2,3,17-β-triol 2-methyl etherGenerator
2-Methoxyestradiol-17bGenerator
2-Methoxyestradiol-17βGenerator
Chemical FormulaC19H26O3
Average Molecular Weight302.4079
Monoisotopic Molecular Weight302.188194698
IUPAC Name(1S,10R,11S,14S,15S)-4-methoxy-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-triene-5,14-diol
Traditional Name2-methoxyestradiol
CAS Registry Number362-07-2
SMILES
[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C(OC)=C3
InChI Identifier
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
InChI KeyInChIKey=CQOQDQWUFQDJMK-SSTWWWIQSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 17-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • Methoxyphenol
  • Anisole
  • Alkyl aryl ether
  • Benzenoid
  • Cyclic alcohol
  • Secondary alcohol
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point189 - 190 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0097 mg/mLALOGPS
logP3.7ALOGPS
logP3.59ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)10.29ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.69 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity86.37 m3·mol-1ChemAxon
Polarizability35.2 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-016s-2792200000-4c8c5cfcb17a537e5130View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0udi-0900000000-51addcf0be873acf4568View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0udi-0900000000-9189876ead18b5520cfcView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0ue9-0900000000-c60cd007c37d58b43c6fView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Prostate
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.01000 +/- 0.00066 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.004 +/- 0.0009 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0010 (0.0033-0.0210) uMAdult (>18 years old)Female
Ovarian cancer
details
Associated Disorders and Diseases
Disease References
Ovarian cancer
  1. Lakhani NJ, Lepper ER, Sparreboom A, Dahut WL, Venitz J, Figg WD: Determination of 2-methoxyestradiol in human plasma, using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19(9):1176-82. [15818726 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022021
KNApSAcK IDNot Available
Chemspider ID59788
KEGG Compound IDC05302
BioCyc IDBACIMETHRIN
BiGG IDNot Available
Wikipedia Link2-Methoxyestradiol
NuGOwiki LinkHMDB00405
Metagene LinkHMDB00405
METLIN ID5394
PubChem Compound66414
PDB IDESM
ChEBI ID28955
References
Synthesis ReferenceZhang, Beina; Wang, Hongbo; Zhang, Qian; Chen, Ying; Xia, Peng. An improved process for synthesis of 2-methoxyestradiol. Fudan Xuebao, Yixueban (2003), 30(5), 494-495.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Schumacher G, Neuhaus P: The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors. J Cancer Res Clin Oncol. 2001 Jul;127(7):405-10. [11469676 ]
  2. Kumar AP, Garcia GE, Slaga TJ: 2-methoxyestradiol blocks cell-cycle progression at G(2)/M phase and inhibits growth of human prostate cancer cells. Mol Carcinog. 2001 Jul;31(3):111-24. [11479920 ]
  3. Lakhani NJ, Lepper ER, Sparreboom A, Dahut WL, Venitz J, Figg WD: Determination of 2-methoxyestradiol in human plasma, using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005;19(9):1176-82. [15818726 ]
  4. Bu S, Blaukat A, Fu X, Heldin NE, Landstrom M: Mechanisms for 2-methoxyestradiol-induced apoptosis of prostate cancer cells. FEBS Lett. 2002 Nov 6;531(2):141-51. [12417302 ]
  5. Pico C, Puigserver P, Oliver P, Palou A: 2-Methoxyestradiol, an endogenous metabolite of 17beta-estradiol, inhibits adipocyte proliferation. Mol Cell Biochem. 1998 Dec;189(1-2):1-7. [9879647 ]
  6. Lakhani NJ, Sparreboom A, Dahut WL, Venitz J, Figg WD: Determination of the antiangiogenesis agent 2-methoxyestradiol in human plasma by liquid chromatography with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jul 5;806(2):289-93. [15171941 ]

Enzymes

General function:
Involved in magnesium ion binding
Specific function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular weight:
30036.77
Reactions
2-Hydroxyestradiol + S-Adenosylmethionine → 2-Methoxyestradiol + S-Adenosylhomocysteinedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme has glucuronidating capacity with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems to be active.
Gene Name:
UGT2B28
Uniprot ID:
Q9BY64
Molecular weight:
38742.9
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
Gene Name:
UGT2B4
Uniprot ID:
P06133
Molecular weight:
60512.035
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in protein methyltransferase activity
Specific function:
Methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in some proteins
Gene Name:
PRMT3
Uniprot ID:
O60678
Molecular weight:
59902.7
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT2B10
Uniprot ID:
P36537
Molecular weight:
60773.485
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. It also catalyzes the glucuronidation of endogenous estrogens and androgens.
Gene Name:
UGT2B15
Uniprot ID:
P54855
Molecular weight:
61035.815
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Active on odorants and seems to be involved in olfaction; it could help clear lipophilic odorant molecules from the sensory epithelium.
Gene Name:
UGT2A1
Uniprot ID:
Q9Y4X1
Molecular weight:
60771.605
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A8
Uniprot ID:
Q9HAW9
Molecular weight:
59741.035
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A3
Uniprot ID:
P35503
Molecular weight:
60337.835
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A10
Uniprot ID:
Q9HAW8
Molecular weight:
59809.075
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The major substrates of this isozyme are eugenol > 4-methylumbelliferone > dihydrotestosterone (DHT) > androstane-3-alpha,17-beta-diol (3-alpha-diol) > testosterone > androsterone (ADT).
Gene Name:
UGT2B17
Uniprot ID:
O75795
Molecular weight:
61094.915
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A6
Uniprot ID:
P19224
Molecular weight:
60750.215
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A5
Uniprot ID:
P35504
Molecular weight:
60070.565
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT2B11
Uniprot ID:
O75310
Molecular weight:
61037.8
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A7
Uniprot ID:
Q9HAW7
Molecular weight:
59818.315
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).
Gene Name:
UGT2A3
Uniprot ID:
Q6UWM9
Molecular weight:
60253.94
Reactions
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphatedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A10
Uniprot ID:
Q5DT02
Molecular weight:
59809.1
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A8
Uniprot ID:
Q5DSZ6
Molecular weight:
59741.0
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
Not Available
Gene Name:
UGT1A7
Uniprot ID:
Q5DSZ7
Molecular weight:
59818.3