2-Methoxyestradiol
2-Methoxyestradiol|
|
| Identifiers |
|---|
- (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  N |
|---|
| PubChem (CID) |
66414 |
|---|
| ChemSpider |
59788  Y |
|---|
| UNII |
6I2QW73SR5 Y |
|---|
| ChEBI |
CHEBI:28955 Y |
|---|
| ChEMBL |
CHEMBL299613 Y |
|---|
| Chemical and physical data |
|---|
| Formula |
C19H26O3 |
|---|
| Molar mass |
302.408 g/mol |
|---|
| 3D model (Jmol) |
Interactive image |
|---|
Oc1cc3c(cc1OC)[C@H]2CC[C@@]4([C@@H](O)CC[C@H]4[C@@H]2CC3)C
|
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 YKey:CQOQDQWUFQDJMK-SSTWWWIQSA-N Y
|
| NY (what is this?) (verify) |
|---|
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
References
- ↑ EntreMed's Product Information Site Archived May 4, 2005, at the Wayback Machine.
- ↑ 2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate. Pribluda VS, et al. Cancer Metastasis Rev. 2000;19(1-2):173-9. Review.
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ "EntreMed Presents Results for Panzem® NCD Phase 2 Ovarian Cancer Study". Archived from the original on July 17, 2012.
- ↑ 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.
- ↑ http://adisinsight.springer.com/drugs/800008361
External links
|
|---|
|
| ER | Agonists |
- Steroidal: 1-Keto-1,2,3,4-tetrahydrophenanthrene
- 3α-Androstanediol
- 3β-Androstanediol
- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- 4-Androstenediol
- 4-Androstenedione
- 4-Hydroxyestradiol
- 4-Hydroxyestrone
- 5-Androstenediol
- 7-Oxo-DHEA
- 7α-Hydroxy-DHEA
- 7β-Hydroxyepiandrosterone
- 8,9-Dehydroestrone
- 8β-VE2
- 16α-Hydroxy-DHEA
- 16α-Hydroxyestrone
- 16α-Iodo-E2
- 16α-LE2
- 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
- 17α-Dihydroequilenin
- 17α-Dihydroequilin
- 17α-Epiestriol (16α-hydroxy-17α-estradiol)
- 17β-Dihydroequilenin
- 17β-Dihydroequilin
- Abiraterone
- Abiraterone acetate
- 17α-Estradiol (alfatradiol)
- Alestramustine
- Almestrone
- Anabolic steroids (e.g., testosterone and esters, methyltestosterone, metandienone (methandrostenolone), nandrolone and esters, many others; via estrogenic metabolites)
- Atrimustine
- Bolandiol
- Bolandiol dipropionate
- Butolame
- Clomestrone
- Cloxestradiol
- DHEA
- DHEA-S
- Digitoxin (digitalis)
- Diosgenin
- Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
- Epimestrol
- Equilenin
- Equilin
- Estetrol
- Estradiol
- Estramustine
- Estramustine phosphate
- Estrapronicate
- Estrazinol
- Estriol
- Estrofurate
- Estromustine
- Estrone
- Etamestrol (eptamestrol)
- Ethinyl estradiol
- Ethinyl estriol
- Etynodiol diacetate
- Guggulsterone
- Hexolame
- Hydroxyestrone diacetate
- Mestranol
- Methylestradiol
- Moxestrol
- Mytatrienediol
- Nilestriol
- Noretynodrel
- Orestrate
- Pentolame
- Phytosterols (e.g., β-sitosterol, campesterol, stigmasterol)
- Polyestradiol phosphate
- Prodiame
- Prolame
- Promestriene
- Quinestradol
- Quinestrol
- Non-steroidal: (R,R)-THC
- (S,S)-THC
- 2,8-DHHHC
- Allenoic acid
- Alternariol
- Anethole
- Anol
- Benzestrol
- Bifluranol
- Biochanin A
- Bisdehydrodoisynolic acid
- Carbestrol
- Chalconoids (e.g., isoliquiritigenin, phloretin, phlorizin (phloridzin), wedelolactone)
- Coumestans (e.g., coumestrol, psoralidin)
- Deoxymiroestrol
- Dianethole
- Dianol
- Diarylpropionitrile
- Dieldrin
- Dienestrol
- Diethylstilbestrol
- Dimestrol (dianisylhexene)
- Dimethylallenolic acid
- Doisynoestrol (fenocycline)
- Doisynolic acid
- Efavirenz
- Endosulfan
- ERB-196 (WAY-202196)
- Estrobin (DBE)
- Fenarimol
- Fenestrel
- FERb 033
- Flavonoids (incl. 7,8-DHF, 8-prenylnaringenin, apigenin, baicalein, baicalin, calycosin, catechin, daidzein, daidzin, ECG, EGCG, epicatechin, equol, formononetin, glabrene, glabridin, genistein, genistin, glycitein, kaempferol, liquiritigenin, mirificin, myricetin, naringenin, pinocembrin, prunetin, puerarin, quercetin, tectoridin, tectorigenin)
- Fosfestrol (diethylstilbestrol diphosphate)
- Furostilbestrol (diethylstilbestrol difuroate)
- GTx-758
- Hexestrol
- ICI-85966 (Stilbostat)
- Lavender oil
- Lignans (e.g., enterodiol, enterolactone)
- Mestilbol
- Metalloestrogens (e.g., cadmium)
- Methallenestril
- Methestrol
- Methestrol dipropionate
- Methiocarb
- Methoxychlor
- Miroestrol
- Nyasol (cis-hinokiresinol)
- Paroxypropione
- Pentafluranol
- Phenestrol
- Photoanethole
- Prinaberel (ERB-041, WAY-202041)
- Propylpyrazoletriol
- Resorcylic acid lactones (e.g., zearalanone, zearalenol, zearalenone, zeranol (α-zearalanol), taleranol (teranol, β-zearalanol))
- Quadrosilan
- SC-4289
- SKF-82,958
- Stilbenoids (e.g., resveratrol)
- Synthetic xenoestrogens (e.g., alkylphenols, bisphenols (e.g., BPA, BPF, BPS), DDT, parabens, PBBs, PHBA, phthalates, PCBs)
- Terfluranol
- WAY-166818
- WAY-200070
- Triphenylchlorethylene
- Triphenylmethylethylene
- WAY-214156
|
|---|
| | |
|---|
| Antagonists | |
|---|
|
|---|
|
| GPER | |
|---|
|
See also: Androgenics • Glucocorticoidics • Mineralocorticoidics • Progestogenics • Steroid hormone metabolism modulators |
