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
SMILES
[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])C=C(O)C(OC)=C4
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
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16985056
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL1783 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26004429 |
0.07 µM [EC50] | ||
Target ID: CHEMBL385 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24923521 |
0.8 µM [IC50] | ||
Target ID: CHEMBL614213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24923521 |
1.2 µM [IC50] | ||
Target ID: CHEMBL2094134 |
2.2 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Dual effect of 2-methoxyestradiol on cell cycle events in human osteosarcoma 143B cells. | 2002 |
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Reduction of post injury neointima formation due to 17beta-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182,780 in vitro. | 2002 Aug 6 |
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Regulation of the activation of nuclear factor kappaB by mitochondrial respiratory function: evidence for the reactive oxygen species-dependent and -independent pathways. | 2002 Dec |
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Introgen obtains key patent obtained for p53-targeted chemotherapy. | 2002 Dec |
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Promising preclinical activity of 2-methoxyestradiol in multiple myeloma. | 2002 Dec |
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Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs. | 2002 Dec |
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2-Methoxyestradiol induces p53-associated apoptosis of colorectal cancer cells. | 2002 Dec 10 |
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Mitochondrial defects in cancer. | 2002 Dec 9 |
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Introduction of a novel proliferation assay for pharmacological studies allowing the combination of BrdU detection and phenotyping. | 2002 Jun 1 |
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Evidence for genomic and nongenomic actions of estrogen in growth plate regulation in female and male rats at the onset of sexual maturation. | 2002 Nov |
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Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol. | 2002 Nov 22 |
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Mechanisms for 2-methoxyestradiol-induced apoptosis of prostate cancer cells. | 2002 Nov 6 |
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The effect of exchanging various substituents at the 2-position of 2-methoxyestradiol on cytotoxicity in human cancer cell cultures and inhibition of tubulin polymerization. | 2002 Oct 10 |
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Evidence that 2-methoxyestradiol suppresses proliferation and accelerates apoptosis in normal rat growth plate chondrocytes. | 2002 Sep |
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Novel therapies for multiple myeloma. | 2002 Sep |
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2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells. | 2002 Sep 15 |
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Estradiol metabolism and malignant disease. | 2002 Sep 30 |
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INGN 201: Ad-p53, Ad5CMV-p53, Adenoviral p53, INGN 101, p53 gene therapy--Introgen, RPR/INGN 201. | 2003 |
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Metabolism of [6,7-3H, 35S] estradiol 17-sulfate in rats. | 2003 Apr |
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Short synthesis of 2-methoxyestradiol and 2-hydroxyestradiol. | 2003 Apr |
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2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. | 2003 Apr |
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Novel 2-methoxyestradiol analogues with antitumor activity. | 2003 Apr 1 |
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Synthesis and evaluation of a novel nonsteroidal-specific endothelial cell proliferation inhibitor. | 2003 Apr 10 |
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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 Aug |
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Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications. | 2003 Aug |
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Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines. | 2003 Aug 1 |
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Opposite regulation of XIAP and Smac/DIABLO in the rat endometrium in response to 17beta-estradiol at estrus. | 2003 Aug 27 |
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Exposure of bovine oocytes to the endogenous metabolite 2-methoxyestradiol during in vitro maturation inhibits early embryonic development. | 2003 Dec |
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Growth inhibition of multi-drug-resistant breast cancer cells by 2-methoxyoestradiol-bis-sulphamate and 2-ethyloestradiol-bis-sulphamate. | 2003 Feb |
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Effect of tamoxifen and 2-methoxyestradiol alone and in combination on human breast cancer cell proliferation. | 2003 Feb |
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2-Methoxyestradiol interferes with NF kappa B transcriptional activity in primitive neuroectodermal brain tumors: implications for management. | 2003 Feb |
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Effect of 2-methoxyestradiol on the growth of methyl-nitroso-urea (MNU)-induced rat mammary carcinoma. | 2003 Jan |
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Novel therapies for multiple myeloma. | 2003 Jan |
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Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. | 2003 Jan 3 |
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Methylation of 2-hydroxyestradiol in isolated organs. | 2003 Jul |
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Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice. | 2003 Jul 7 |
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Structure/function analyses of human sex hormone-binding globulin: effects of zinc on steroid-binding specificity. | 2003 Jun |
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Roles of p38- and c-jun NH2-terminal kinase-mediated pathways in 2-methoxyestradiol-induced p53 induction and apoptosis. | 2003 Jun |
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Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. | 2003 Jun 15 |
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Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. | 2003 Jun 16 |
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Angiogenesis inhibition with TNP-470, 2-methoxyestradiol, and paclitaxel in experimental pancreatic carcinoma. | 2003 Mar |
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Identification of a novel Bcl-xL phosphorylation site regulating the sensitivity of taxol- or 2-methoxyestradiol-induced apoptosis. | 2003 Mar 13 |
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2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production. | 2003 May 1 |
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Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays. | 2003 May 1 |
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Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. | 2003 May 15 |
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The nonsteroidal effects of diethylstilbestrol: the rationale for androgen deprivation therapy without estrogen deprivation in the treatment of prostate cancer. | 2003 Nov |
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Neuroprotective and neurotoxic effects of estrogens. | 2003 Nov 14 |
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Catecholamines block the antimitogenic effect of estradiol on human glomerular mesangial cells. | 2003 Sep |
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Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells. | 2003 Sep 18 |
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Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. | 2003 Sep 26 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00592579
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16985056
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.
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FDA ORPHAN DRUG |
202905
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NCI_THESAURUS |
C1821
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FDA ORPHAN DRUG |
201405
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FDA ORPHAN DRUG |
143801
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FDA ORPHAN DRUG |
224006
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NCI_THESAURUS |
C843
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66414
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2-METHOXYESTRADIOL
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C022830
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6I2QW73SR5
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C965
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ACTIVE MOIETY