Surf Wiki
Save to docs
arts/music

From Surf Wiki (app.surf) — the open knowledge base

2-Methoxyestradiol

Chemical compound

Chemical compound

| elimination_half-life =

2-Methoxyestradiol (2-ME2, 2-MeO-E2) is a natural metabolite of estradiol and 2-hydroxyestradiol (2-OHE2). It is specifically the 2-methyl ether of 2-hydroxyestradiol. 2-Methoxyestradiol prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis), hence it is an angiogenesis inhibitor. It also acts as a vasodilator and induces apoptosis in some cancer cell lines. 2-Methoxyestradiol is derived from estradiol, although it interacts poorly with the estrogen receptors (2,000-fold lower activational potency relative to estradiol). However, it retains activity as a high-affinity agonist of the G protein-coupled estrogen receptor (GPER) (10 nM, relative to 3–6 nM for estradiol). It can also be used to treat alveolar echinococcosis when combined with albendazole.

Clinical development

2-Methoxyestradiol was being developed as an experimental drug candidate with the tentative brand name Panzem. 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.

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

, all clinical development of 2-methoxyestradiol has been suspended or discontinued. This is significantly due to the very poor oral bioavailability of the molecule and also due to its extensive metabolism. Analogues have been developed in an attempt to overcome these problems. An example is 2-methoxyestradiol disulfamate (STX-140), the C3 and C17β disulfamate ester of 2-methoxyestradiol.

Clinical effects

2-Methoxyestradiol was found to increase sex hormone-binding globulin (SHBG) levels in men by 2.5-fold at a dose of 400 mg/day and by 4-fold at a dose of 1,200 mg/day. Conversely, it did not seem to suppress testosterone levels.

A study in 2000 indicated that 2-Methoxyestradiol induces G2/M cycle arrest, apoptosis and the disruption of thyroid follicles. This process results in the release of thyroid antigens that may play a role in high incidence of thyroid autoantibodies and autoimmune thyroid disease in women.

References

References

  1. (2000). "2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate". Cancer and Metastasis Reviews.
  2. (April 2012). "Pharmacologic effects of 2-methoxyestradiol on angiotensin type 1 receptor down-regulation in rat liver epithelial and aortic smooth muscle cells". Gender Medicine.
  3. (January 2003). "2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway". Cancer Research.
  4. (March 2003). "Dose-response effects of 2-methoxyestradiol on estrogen target tissues in the ovariectomized rat". Endocrinology.
  5. (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacological Reviews.
  6. (2016). "Estrogen Receptors". Springer.
  7. "EntreMed's Statistics". EntreMed, Inc..
  8. (February 2009). "Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies". Clinical Cancer Research.
  9. "EntreMed Presents Results for Panzem NCD Phase 2 Ovarian Cancer Study".
  10. (February 2003). "2-Methoxyestradiol, a promising anticancer agent". Pharmacotherapy.
  11. (September 2005). "Effects of hormone deprivation and 2-methoxyestradiol combination therapy on hormone-dependent prostate cancer in vivo". Neoplasia.
  12. "2-Methoxyestradiol - CASI Pharmaceuticals". Springer Nature Switzerland AG.
  13. (August 2018). "SULFATION PATHWAYS: Steroid sulphatase inhibition via aryl sulphamates: clinical progress, mechanism and future prospects". Journal of Molecular Endocrinology.
  14. (September 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". Clinical Cancer Research.
  15. (July 2000). "2-Methoxyestradiol, an endogenous estrogen metabolite, induces thyroid cell apoptosis". Molecular and Cellular Endocrinology.
Info: Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

abandoned-drugs angiogenesis-inhibitors antineoplastic-drugs estranes ethers gper-agonists human-metabolites lipid-lowering-agents microtubule-inhibitors mitotic-inhibitors hydroxyarenes
Want to explore this topic further?

Ask Mako anything about 2-Methoxyestradiol — get instant answers, deeper analysis, and related topics.

Research with Mako

Free with your Surf account

Content sourced from Wikipedia, available under CC BY-SA 4.0.

This content may have been generated or modified by AI. CloudSurf Software LLC is not responsible for the accuracy, completeness, or reliability of AI-generated content. Always verify important information from primary sources.

Report