2-Methoxyestradiol

2-Methoxyestradiol

Identifiers
IUPAC name (8R,9S,13S,14S,17S)-2-Methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
Synonyms	2-Methoxyestra-1,3,5(10)-triene-3,17β-diol
CAS Number	362-07-2
PubChem (CID)	66414
ChemSpider	59788
UNII	6I2QW73SR5
ChEBI	CHEBI:28955
ChEMBL	CHEMBL299613
Chemical and physical data
Formula	C19H26O3
Molar mass	302.408 g/mol
3D model (Jmol)	Interactive image
SMILES Oc1cc3c(cc1OC)[C@H]2CC[C@@]4([C@@H](O)CC[C@H]4[C@@H]2CC3)C
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 Key:CQOQDQWUFQDJMK-SSTWWWIQSA-N
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2-Methoxyestradiol (2-ME2) is a natural metabolite of estradiol. As an experimental drug candidate, it is being developed under the tradename of Panzem.^[1] It prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis), hence it is an angiogenesis inhibitor.^[2]

It also acts as a vasodilator.

2-ME2 is derived from estradiol, although it binds poorly (2000-fold lower activational potency) to known estrogen receptors.^[3] However, 2-ME2 retains activity as a high-affinity agonist of the GPER (GPR30).^[4]

It induces apoptosis in some cancer cell lines.^[5]

It has undergone Phase 1 clinical trials against breast cancer.

A phase II trial of 18 advanced ovarian cancer patients reported encouraging results in Oct 2007.^[6]

Preclinical models also suggest that 2-ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. Several studies have been conducted showing 2-ME2 is a microtubule-inhibitor^[7] and effective against prostate cancer in rodents.

As of 2015, all clinical development of 2-ME2 has been suspended or discontinued.^[8]

See also

• 2-Hydroxyestradiol
• 17α-Epiestriol
• MP-2001

References

1. EntreMed's Product Information Site Archived May 4, 2005, at the Wayback Machine.
2. 2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate. Pribluda VS, et al. Cancer Metastasis Rev. 2000;19(1-2):173-9. Review.
3. Dose-response effects of 2-methoxyestradiol on estrogen target tissues in the ovariectomized rat. Sibonga JD et al. Endocrinology. 2003 Mar;144(3):785-92. PMID 12586754
4. Thekkumkara, Thomas; Snyder, Russell; Karamyan, Vardan T. (2016). "Competitive Binding Assay for the G-Protein-Coupled Receptor 30 (GPR30) or G-Protein-Coupled Estrogen Receptor (GPER)". 1366: 11–17. doi:10.1007/978-1-4939-3127-9_2. ISSN 1064-3745.
5. LaValee; et al. (2003). "2-Methoxyestradiol Up-Regulates Death Receptor 5 and Induces Apoptosis through Activation of the Extrinsic Pathway". 63 (2): 468–75. PMID 12543804.
6. "EntreMed Presents Results for Panzem® NCD Phase 2 Ovarian Cancer Study". Archived from the original on July 17, 2012.
7. Lakhani, NJ; Sarkar, MA; Venitz, J; Figg, WD (2003). "2-Methoxyestradiol, a promising anticancer agent". Pharmacotherapy. 23 (2): 165–72. doi:10.1592/phco.23.2.165.32088. PMID 12587805.
8. http://adisinsight.springer.com/drugs/800008361

External links

• Chemical Information and Structure from the Comparative Toxicogenomics Database
• 2-Methoxyestradiol 4 journal refs as URLs