2-METHOXYESTRADIOL

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H26O3
Molecular Weight	302.4079
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(O)C=C2CC[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]3C2=C1

InChI

InChIKey=CQOQDQWUFQDJMK-SSTWWWIQSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H26O3
Molecular Weight	302.4079
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugbank.ca/drugs/DB02342 | https://www.ncbi.nlm.nih.gov/pubmed/27020471
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16985056

2-Methoxyestradiol (2ME2) is a natural metabolite of endogenous estrogen hormone 17β-estradiol in human and devoid of estrogenic activity. It 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. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. 2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. 2-Methoxyestradiol shows strong cytotoxic effect on estrogen dependent and independent cancerous cells, which is mainly due to disruption of microtubule process and p53 induced apoptosis through caspase, reactive oxygen species (ROS), superoxide dismutase (SOD) and nitric oxide synthase. 2-Methoxyestradiol inhibits tubulin polymerisation by binding to colchicine binding site of the tubulin and arrests cell cycle at G2/M-phase.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor A 3 Target ID: CHEMBL1783 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26004429	Inhibitor 8504	0.07 µM [EC50]
K562 4 Target ID: CHEMBL385 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24923521	Inhibitor 8504	0.8 µM [IC50]
OVCAR-3 1 Target ID: CHEMBL614213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24923521	Inhibitor 8504	1.2 µM [IC50]
Tubulin 69 Target ID: CHEMBL2094134 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24923521 \| https://www.ncbi.nlm.nih.gov/pubmed/9240348 \| https://www.ncbi.nlm.nih.gov/pubmed/16985056	Inhibitor 8504	2.2 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00592579	Primary	Phase II 1147	Unknown Approved Use Unknown
Recurrent glioblastoma multiforme 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00306618	Primary	Phase II 1147	Unknown Approved Use Unknown
Metastatic renal cell carcinoma 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00444314	Primary	Phase II 1147	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT00394810	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5.6 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.9 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
49.7 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46.2 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16969706	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		2-METHOXYESTRADIOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.7% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/?term=16940808			2-METHOXYESTRADIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0038EZ	https://www.1pchem.com/search?query=1P0038EZ
A2B Chem	AB50075	http://a2bchem.com/prod/AB50075
AK Scientific	X5011	https://aksci.com/item_detail.php?cat=X5011
ApexBio Technology	A4188	https://www.apexbt.com/catalogsearch/result/?q=A4188
AstaTech	C74863	http://astatechinc.com/CPSResult.php?CRNO=C74863
Cayman Chemical	13021	http://www.caymanchem.com/app/template/Product.vm/catalog/13021
Chem Scene	CS-0176	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0176
ChemShuttle	151396	https://www.chemshuttle.com/catalogsearch/result/?q=151396
eMolecules	108761904	https://orderbb.emolecules.com/search/#?query=108761904
eMolecules	261737267	https://orderbb.emolecules.com/search/#?query=261737267
eMolecules	29543350	https://orderbb.emolecules.com/search/#?query=29543350
eMolecules	300008558	https://orderbb.emolecules.com/search/#?query=300008558
eMolecules	486062	https://orderbb.emolecules.com/search/#?query=486062
eNovation Chemicals	D584542	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D584542&searchbtn.x=0&searchbtn.y=0
Hairui	HR119693	http://www.hairuichem.com/en/product/search.do?q=HR119693
KeyOrganics	AS-19175	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19175
Lab Network	LN01303091	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01303091
Lab Seeker	SC-27817	http://www.labseeker.com/search.php?keywords=SC-27817&category=0
LabSeeker	SC-27817	http://www.labseeker.com/search.php?keywords=SC-27817&category=0
mcule	MCULE-4679844983	https://mcule.com/MCULE-4679844983/
mcule	MCULE-6710800946	https://mcule.com/MCULE-6710800946/
MedChem Express	HY-12033	https://www.medchemexpress.com/search.html?q=HY-12033&ft=&fa=&fp=
Molnova	M14242	https://www.molnova.com/en/serch-list.html?keywords=M14242
MolPort	MolPort-003-927-295	https://www.molport.com/shop/molecule-link/MolPort-003-927-295
MuseChem	I003330	https://www.musechem.com/product/I003330.html
Ryan Scientific	Phthalic_Acid_Monobenzyl_Ester	https://ryansci.com/products?q=Phthalic_Acid_Monobenzyl_Ester&list_q=&search_type=exact
ShangHai Biochempartner	BCP000235	http://www.biochempartner.com/search_BCP000235
ShangHai Biochempartner	BCP02076	http://www.biochempartner.com/search_BCP02076
TargetMol	362-07-2	https://www.targetmol.com/search?keyword=362-07-2
TargetMol	HMDB0000405	https://www.targetmol.com/search?keyword=HMDB0000405
TargetMol	T2220	https://www.targetmol.com/search?keyword=T2220
Tocris	1807	https://www.tocris.com/search.php?Type=QuickSearch&Value=1807
Toronto Research Chemicals	M262625	https://www.trc-canada.com/product-detail/?CatNum=M262625

PubMed

Title	Date	PubMed
Exposure of bovine oocytes to the endogenous metabolite 2-methoxyestradiol during in vitro maturation inhibits early embryonic development.	2003-12	12890717
Neuroprotective and neurotoxic effects of estrogens.	2003-11-14	14568325
The nonsteroidal effects of diethylstilbestrol: the rationale for androgen deprivation therapy without estrogen deprivation in the treatment of prostate cancer.	2003-11	14532759
Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism.	2003-09-26	12853461
Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells.	2003-09-18	13679868
Catecholamines block the antimitogenic effect of estradiol on human glomerular mesangial cells.	2003-09	12913061
Opposite regulation of XIAP and Smac/DIABLO in the rat endometrium in response to 17beta-estradiol at estrus.	2003-08-27	12967350
Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines.	2003-08-01	12902195
The effects of 2-methoxy oestrogens and their sulphamoylated derivatives in conjunction with TNF-alpha on endothelial and fibroblast cell growth, morphology and apoptosis.	2003-08	14568571
Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications.	2003-08	12815276
Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice.	2003-07-07	12838326
2-methoxyestradiol alters cell motility, migration, and adhesion.	2003-07-01	12637335
Methylation of 2-hydroxyestradiol in isolated organs.	2003-07	12771046
Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11.	2003-06-16	12799646
Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1.	2003-06-15	12810639
Structure/function analyses of human sex hormone-binding globulin: effects of zinc on steroid-binding specificity.	2003-06	12943704
Roles of p38- and c-jun NH2-terminal kinase-mediated pathways in 2-methoxyestradiol-induced p53 induction and apoptosis.	2003-06	12807754
Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents.	2003-05-15	12531810
2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production.	2003-05-01	12730670
Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays.	2003-05-01	12480690
Synthesis and evaluation of a novel nonsteroidal-specific endothelial cell proliferation inhibitor.	2003-04-10	12672229
Novel 2-methoxyestradiol analogues with antitumor activity.	2003-04-01	12670902
Metabolism of [6,7-3H, 35S] estradiol 17-sulfate in rats.	2003-04	12787901
Short synthesis of 2-methoxyestradiol and 2-hydroxyestradiol.	2003-04	12787899
Novel therapies in multiple myeloma.	2003-04	12731664
2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF.	2003-04	12726862
Cell cycle block and apoptosis induction in a human melanoma cell line following treatment with 2-methoxyoestradiol: therapeutic implications?	2003-04	12690294
IDN 5390: an oral taxane candidate for protracted treatment schedules.	2003-03-24	12644838
Identification of a novel Bcl-xL phosphorylation site regulating the sensitivity of taxol- or 2-methoxyestradiol-induced apoptosis.	2003-03-13	12633850
CYP450- and COMT-derived estradiol metabolites inhibit activity of human coronary artery SMCs.	2003-03	12624000
Angiogenesis inhibition with TNP-470, 2-methoxyestradiol, and paclitaxel in experimental pancreatic carcinoma.	2003-03	12604915
In vitro effects of catecholamines and catecholestrogens on brain tyrosine hydroxylase activity and kinetics in the female catfish Heteropneustes fossilis.	2003-03	12588516
Dose-response effects of 2-methoxyestradiol on estrogen target tissues in the ovariectomized rat.	2003-03	12586754
Medical hypothesis: hyperhomocysteinemia is a risk factor for estrogen-induced hormonal cancer.	2003-03	12579301
Inhibition of MCF-7 breast cancer cell proliferation and in vivo steroid sulphatase activity by 2-methoxyoestradiol-bis-sulphamate.	2003-02	12711022
The effects of 2-substituted oestrogen sulphamates on the growth of prostate and ovarian cancer cells.	2003-02	12711018
Growth inhibition of multi-drug-resistant breast cancer cells by 2-methoxyoestradiol-bis-sulphamate and 2-ethyloestradiol-bis-sulphamate.	2003-02	12711013
Effect of tamoxifen and 2-methoxyestradiol alone and in combination on human breast cancer cell proliferation.	2003-02	12711011
2-Methoxyestradiol, a promising anticancer agent.	2003-02	12587805
2-Methoxyestradiol interferes with NF kappa B transcriptional activity in primitive neuroectodermal brain tumors: implications for management.	2003-02	12584169
2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway.	2003-01-15	12543804
The effect of endogenous estradiol metabolites on the proliferation of human breast cancer cells.	2003-01-10	12493568
Effect of 2-methoxyestradiol on the growth of methyl-nitroso-urea (MNU)-induced rat mammary carcinoma.	2003-01	12648524
Novel therapies for multiple myeloma.	2003-01	12492571
INGN 201: Ad-p53, Ad5CMV-p53, Adenoviral p53, INGN 101, p53 gene therapy--Introgen, RPR/INGN 201.	2003	12749760
Mitochondrial defects in cancer.	2002-12-09	12513701
Regulation of the activation of nuclear factor kappaB by mitochondrial respiratory function: evidence for the reactive oxygen species-dependent and -independent pathways.	2002-12	12573143
Introgen obtains key patent obtained for p53-targeted chemotherapy.	2002-12	12503203
Promising preclinical activity of 2-methoxyestradiol in multiple myeloma.	2002-12	12473611
Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs.	2002-12	12441194

Patents

Sample Use Guides

In Vivo Use Guide

For Multiple Myeloma treatment: 800 mg of 2ME2 (capsules) administered orally every 12 hours for a total daily dose of 1600 mg.

Route of Administration: Oral

In Vitro Use Guide

In vitro, 2-Methoxyestradiol (5-100 umol/L) inhibited assembly of purified tubulin in a concentration-dependent manner, with maximal inhibition (60%) at 200 umol/L 2-Methoxyestradiol.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:04:43 GMT 2025` Edited by `admin` on `Mon Mar 31 18:04:43 GMT 2025`
Record UNII	6I2QW73SR5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-659853

Preferred Name

English

2-METHOXYESTRADIOL

Common Name

English

2-Methoxyestradiol [WHO-DD]

Common Name

English

(17.BETA.)-2-METHOXYESTRA-1,3,5(10)-TRIENE-3,17-DIOL

Systematic Name

English

2-METHOXYOESTRADIOL [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

202905