Identification
- Generic Name
- 2-Methoxyestradiol
- DrugBank Accession Number
- DB02342
- Background
2-Methoxyestradiol (2ME2) is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers and preclinical studies suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for 2-Methoxyestradiol (DB02342)
- Weight
- Average: 302.4079
Monoisotopic: 302.188194698 - Chemical Formula
- C19H26O3
- Synonyms
- 2-Hydroxyestradiol 2-methyl ether
- 2-Hydroxyestradol 2-methyl ether
- 2-ME2
- 2-methoxy-17β-estradiol
- 2-Methoxyestradiol-17beta
- 2ME2
Pharmacology
- Indication
For the treatment of breast cancer and inflammatory diseases such as rheumatoid arthritis.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
2-Methoxyestradiol belongs to the family of drugs called angiogenesis inhibitors. It also acts as a vasodilator.
- Mechanism of action
2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. 2-methoxyestradiol is a naturally occurring estrogen metabolite but has no undesired estrogenic activity.
Target Actions Organism UCatechol O-methyltransferase Not Available Humans UCytochrome P450 1A1 Not Available Humans UCytochrome P450 1B1 Not Available Humans UCytochrome P450 19A1 Not Available Humans UHypoxia-inducible factor 1-alpha Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
2ME2 was found to bind in decreasing order to plasma>albumin>alpha1-acid glycoprotein>sex-hormone-binding globulin. Plasma concentration-time profiles of total 2ME2 and unbound 2ME2 concentrations in a patient with cancer receiving 2ME2 as a single oral dose were parallel to each other. Thus, indicating that plasma protein binding is not an important consideration in pharmacokinetic monitoring of 2ME2.
- Metabolism
In vivo metabolism, assessed using 24-h collections of urine from cancer patients treated with 2ME2 revealed that <0.01% of the total administered dose of 2ME2 is excreted unchanged in urine and about 1% excreted as glucuronides. Collectively, this suggests that glucuronidation and subsequent urinary excretion are elimination pathways for 2ME2.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when 2-Methoxyestradiol is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when 2-Methoxyestradiol is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when 2-Methoxyestradiol is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when 2-Methoxyestradiol is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when 2-Methoxyestradiol is combined with Bupivacaine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Panzem / Panzem NCD / Pulmolar
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6I2QW73SR5
- CAS number
- 362-07-2
- InChI Key
- CQOQDQWUFQDJMK-SSTWWWIQSA-N
- 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
- IUPAC Name
- (1S,3aS,3bR,9bS,11aS)-8-methoxy-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-diol
- 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
References
- General References
- Schumacher G, Hoffmann J, Cramer T, Spinelli A, Jacob D, Bahra M, Pratschke J, Pfitzmann R, Schmidt S, Lage H: Antineoplastic activity of 2-methoxyestradiol in human pancreatic and gastric cancer cells with different multidrug-resistant phenotypes. J Gastroenterol Hepatol. 2007 Sep;22(9):1469-73. Epub 2007 Jul 20. [Article]
- Sutherland TE, Anderson RL, Hughes RA, Altmann E, Schuliga M, Ziogas J, Stewart AG: 2-Methoxyestradiol--a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discov Today. 2007 Jul;12(13-14):577-84. Epub 2007 Jun 26. [Article]
- Fong YC, Yang WH, Hsu SF, Hsu HC, Tseng KF, Hsu CJ, Lee CY, Scully SP: 2-methoxyestradiol induces apoptosis and cell cycle arrest in human chondrosarcoma cells. J Orthop Res. 2007 Aug;25(8):1106-14. [Article]
- Eichenlaub-Ritter U, Winterscheidt U, Vogt E, Shen Y, Tinneberg HR, Sorensen R: 2-methoxyestradiol induces spindle aberrations, chromosome congression failure, and nondisjunction in mouse oocytes. Biol Reprod. 2007 May;76(5):784-93. Epub 2007 Jan 17. [Article]
- Lakhani NJ, Sparreboom A, Xu X, Veenstra TD, Venitz J, Dahut WL, Figg WD: Characterization of in vitro and in vivo metabolic pathways of the investigational anticancer agent, 2-methoxyestradiol. J Pharm Sci. 2007 Jul;96(7):1821-31. [Article]
- Lakhani N, Sparreboom A, Venitz J, Dahut WL, Figg WD: Plasma protein binding of the investigational anticancer agent 2-methoxyestradiol. Anticancer Drugs. 2006 Sep;17(8):977-83. [Article]
- Lakhani NJ, Sarkar MA, Venitz J, Figg WD: 2-Methoxyestradiol, a promising anticancer agent. Pharmacotherapy. 2003 Feb;23(2):165-72. [Article]
- External Links
- Human Metabolome Database
- HMDB0000405
- KEGG Compound
- C05302
- PubChem Compound
- 16760554
- PubChem Substance
- 175426854
- ChemSpider
- 59788
- BindingDB
- 50060957
- ChEBI
- 28955
- ChEMBL
- CHEMBL299613
- ZINC
- ZINC000003818826
- PharmGKB
- PA13496724
- PDBe Ligand
- ESM
- Wikipedia
- 2-Methoxyestradiol
- PDB Entries
- 1lhw
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Carcinoid Tumors 1 2 Completed Treatment Metastatic Renal Cell Carcinoma ( mRCC) 1 2 Completed Treatment Ovarian Cancer 1 2 Completed Treatment Plateau Phase Multiple Myeloma / Relapsed Multiple Myeloma 1 2 Completed Treatment Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00968 mg/mL ALOGPS logP 3.7 ALOGPS logP 3.59 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 10.29 Chemaxon pKa (Strongest Basic) -0.88 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 49.69 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 86.37 m3·mol-1 Chemaxon Polarizability 35.2 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9952 Blood Brain Barrier + 0.8506 Caco-2 permeable + 0.8415 P-glycoprotein substrate Substrate 0.7829 P-glycoprotein inhibitor I Non-inhibitor 0.7228 P-glycoprotein inhibitor II Non-inhibitor 0.817 Renal organic cation transporter Non-inhibitor 0.8176 CYP450 2C9 substrate Non-substrate 0.7967 CYP450 2D6 substrate Non-substrate 0.8076 CYP450 3A4 substrate Substrate 0.7532 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9345 CYP450 2C19 inhibitor Non-inhibitor 0.8521 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8483 Ames test Non AMES toxic 0.8878 Carcinogenicity Non-carcinogens 0.9109 Biodegradation Not ready biodegradable 0.9879 Rat acute toxicity 1.8598 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.965 hERG inhibition (predictor II) Inhibitor 0.7189
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.3108702 predictedDarkChem Lite v0.1.0 [M-H]- 184.3913702 predictedDarkChem Lite v0.1.0 [M-H]- 182.61668 predictedDeepCCS 1.0 (2019) [M+H]+ 186.4690702 predictedDarkChem Lite v0.1.0 [M+H]+ 185.8527702 predictedDarkChem Lite v0.1.0 [M+H]+ 185.01224 predictedDeepCCS 1.0 (2019) [M+Na]+ 183.9649702 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.1157702 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.92476 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- O-methyltransferase activity
- 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-DOP...
- Gene Name
- COMT
- Uniprot ID
- P21964
- Uniprot Name
- Catechol O-methyltransferase
- Molecular Weight
- 30036.77 Da
References
- Parvez S, Parvez SH, Youdim MB: Variation in activity of monoamine metabolizing enzymes in rat liver during pregnancy. Br J Pharmacol. 1975 Feb;53(2):241-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Dawling S, Roodi N, Parl FF: Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. Cancer Res. 2003 Jun 15;63(12):3127-32. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Dawling S, Roodi N, Parl FF: Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. Cancer Res. 2003 Jun 15;63(12):3127-32. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Oxygen binding
- Specific Function
- Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
- Gene Name
- CYP19A1
- Uniprot ID
- P11511
- Uniprot Name
- Aromatase
- Molecular Weight
- 57882.48 Da
References
- Purohit A, Singh A, Ghilchik MW, Reed MJ: Inhibition of tumor necrosis factor alpha-stimulated aromatase activity by microtubule-stabilizing agents, paclitaxel and 2-methoxyestradiol. Biochem Biophys Res Commun. 1999 Jul 22;261(1):214-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transp...
- Gene Name
- HIF1A
- Uniprot ID
- Q16665
- Uniprot Name
- Hypoxia-inducible factor 1-alpha
- Molecular Weight
- 92669.595 Da
References
- Zhou D, Matchett GA, Jadhav V, Dach N, Zhang JH: The effect of 2-methoxyestradiol, a HIF-1 alpha inhibitor, in global cerebral ischemia in rats. Neurol Res. 2008 Apr;30(3):268-71. Epub 2007 Aug 22. [Article]
- Dai Y, Xu M, Wang Y, Pasha Z, Li T, Ashraf M: HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol. 2007 Jun;42(6):1036-44. Epub 2007 Apr 6. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Androgen binding
- Specific Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
Drug created at June 13, 2005 13:24 / Updated at January 14, 2023 19:03