2-Methoxyestradiol   Click here for help

GtoPdb Ligand ID: 12058

Synonyms: 2-ME2 | 2-MeO-E2 | 2ME2 | NSC-659853 | Panzem®
PDB Ligand
Comment: 2-Methoxyestradiol is a high-affinity agonist of the G protein-coupled estrogen receptor (GPER) [6,9]. It is an endogenous metabolite of estradiol (17β-estradiol) and 2-hydroxyestradiol. 2-Methoxyestradiol has anti-angogenic and vasodilatory activities [3-5], but it has limited oral bioavailability [1,7] and failed to show significant efficacy in clinical trials.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 1
Hydrogen bond donors 2
Rotatable bonds 1
Topological polar surface area 49.69
Molecular weight 302.19
XLogP 3.88
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2([C@H]1CC[C@@H]2O)C
Isomeric SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCc1cc(c(cc31)OC)O
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
1. Dahut WL, Lakhani NJ, Gulley JL, Arlen PM, Kohn EC, Kotz H, McNally D, Parr A, Nguyen D, Yang SX et al.. (2006)
Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors.
Cancer Biol Ther, 5 (1): 22-7. [PMID:16357512]
2. Koganti S, Snyder R, Gumaste U, Karamyan VT, Thekkumkara T. (2014)
2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT(1) receptor.
Eur J Pharmacol, 723: 131-40. [PMID:24262995]
3. Koganti S, Snyder R, Thekkumkara T. (2012)
Pharmacologic effects of 2-methoxyestradiol on angiotensin type 1 receptor down-regulation in rat liver epithelial and aortic smooth muscle cells.
Gend Med, 9 (2): 76-93. [PMID:22366193]
4. Lakhani NJ, Sarkar MA, Venitz J, Figg WD. (2003)
2-Methoxyestradiol, a promising anticancer agent.
Pharmacotherapy, 23 (2): 165-72. [PMID:12587805]
5. Pribluda VS, Gubish Jr ER, Lavallee TM, Treston A, Swartz GM, Green SJ. (2000)
2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate.
Cancer Metastasis Rev, 19 (1-2): 173-9. [PMID:11191057]
6. Prossnitz ER, Arterburn JB. (2015)
International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators.
Pharmacol Rev, 67 (3): 505-40. [PMID:26023144]
7. Sidor C, D'Amato R, Miller KD. (2005)
The potential and suitability of 2-methoxyestradiol in cancer therapy.
Clin Cancer Res, 11 (16): 6094-5. [PMID:16115955]
8. Sweeney C, Liu G, Yiannoutsos C, Kolesar J, Horvath D, Staab MJ, Fife K, Armstrong V, Treston A, Sidor C et al.. (2005)
A phase II multicenter, randomized, double-blind, safety trial assessing the pharmacokinetics, pharmacodynamics, and efficacy of oral 2-methoxyestradiol capsules in hormone-refractory prostate cancer.
Clin Cancer Res, 11 (18): 6625-33. [PMID:16166441]
9. Thekkumkara T, Snyder R, Karamyan VT. (2016)
Competitive Binding Assay for the G-Protein-Coupled Receptor 30 (GPR30) or G-Protein-Coupled Estrogen Receptor (GPER).
Methods Mol Biol, 1366: 11-17. [PMID:26585123]