2-Methoxyestradiol

2-Methoxyestradiol
Clinical data
Synonyms 2-Methoxyestra-1,3,5(10)-triene-3,17β-diol
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
ECHA InfoCard 100.164.606
Chemical and physical data
Formula C19H26O3
Molar mass 302.408 g/mol
3D model (JSmol)
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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 October 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

References

  1. EntreMed's Product Information Site Archived May 4, 2005, at the Wayback Machine.
  2. Pribluda VS, Gubish ER, Lavallee TM, Treston A, Swartz GM, Green SJ (2000). "2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate". Cancer Metastasis Reviews. 19 (1-2): 173–9. doi:10.1023/a:1026543018478. PMID 11191057.
  3. Sibonga JD, Lotinun S, Evans GL, Pribluda VS, Green SJ, Turner RT (March 2003). "Dose-response effects of 2-methoxyestradiol on estrogen target tissues in the ovariectomized rat". Endocrinology. 144 (3): 785–92. doi:10.1210/en.2002-220632. PMID 12586754.
  4. 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 in Molecular Biology. 1366: 11–7. doi:10.1007/978-1-4939-3127-9_2. PMID 26585123.
  5. LaVallee TM, Zhan XH, Johnson MS, Herbstritt CJ, Swartz G, Williams MS, Hembrough WA, Green SJ, Pribluda VS (January 2003). "2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway". Cancer Research. 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 (February 2003). "2-Methoxyestradiol, a promising anticancer agent". Pharmacotherapy. 23 (2): 165–72. doi:10.1592/phco.23.2.165.32088. PMID 12587805.
  8. "2-Methoxyestradiol - CASI Pharmaceuticals". Adis Insight. Retrieved 2 March 2017.
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