2-methoxyestradiol 2-methoxyestradiol 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). selected biological properties of endogenous estrogens in rats estrogener rba (%)uterine weight (%)uterotrophylh levels (%)shbg rba (%) control–100–100– estradiol (e2)100506 ± 20+++12–19100 estrone (e1)11 ± 8490 ± 22+++ ?20 estriol (e3)10 ± 4468 ± 30+++8–183 estetrol (e4)0.5 ± 0.2 ?inactive ?1 17α-estradiol4.2 ± 0.8 ? ? ? ? 2-hydroxyestradiol24 ± 7285 ± 8+b31–6128 2-methoxyestradiol0.05 ± 0.04101inactive ?130 4-hydroxyestradiol45 ± 12 ? ? ? ? 4-methoxyestradiol1.3 ± 0.2260++ ?9 4-fluoroestradiola180 ± 43 ?+++ ? ? 2-hydroxyestrone1.9 ± 0.8130 ± 9inactive110–1428 2-methoxyestrone0.01 ± 0.00103 ± 7inactive95–100120 4-hydroxyestrone11 ± 4351++21–5035 4-methoxyestrone0.13 ± 0.04338++65–9212 16α-hydroxyestrone2.8 ± 1.0552 ± 42+++7–24<0.5 2-hydroxyestriol0.9 ± 0.3302+b ? ? 2-methoxyestriol0.01 ± 0.00 ?inactive ?4 notes: values are mean ± sd or range. er rba = relative binding affinity to estrogen receptors of rat uterine cytosol. uterine weight = percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously implanted osmotic pumps. lh levels = luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant. footnotes: a = synthetic (i.e., not endogenous). b = atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). sources: see template. 2-methoxyestradiolclinical datatrade namespanzemother names2-me2; 2-meo-e2; 2-meoe2; 2-hydroxyestradiol 2-methyl ether; 2-methoxyestra-1,3,5(10)-triene-3,17β-diolidentifiers iupac name (8r,9s,13s,14s,17s)-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopentaphenanthrene-3,17-diol cas number362-07-2 npubchem cid66414chemspider59788 yunii6i2qw73sr5chebichebi:28955 ychemblchembl299613 ycomptox dashboard (epa)dtxsid3040938 echa infocard100.164.606 chemical and physical dataformulac19h26o3molar mass302.414 g·mol−13d model (jsmol)interactive image smiles oc1cc3c(cc1oc)2cc4((o)cc42cc3)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 ykey:cqoqdqwufqdjmk-sstwwwiqsa-n y ny (what is this?) (verify) 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. as of 2015, 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.