WAbiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth.
WAcefluranol, also known as 2,3-bis(3,4-diacetoxy-5-fluorophenyl)pentane, is a nonsteroidal antiestrogen of the stilbestrol group that was never marketed. It is a polyfluorinated biphenyl that is related to polybrominated and polychlorinated biphenyls and diethylstilbestrol.
WAmphenone B, or simply amphenone, also known as 3,3-bis(p-aminophenyl)butan-2-one, is an inhibitor of steroid hormone and thyroid hormone biosynthesis which was never marketed but has been used as a tool in scientific research to study corticosteroids and the adrenal glands. It acts as competitive inhibitor of 11β-hydroxylase, 17α-hydroxylase, 17,20-lyase, 21-hydroxylase, and 3β-hydroxysteroid dehydrogenase, as well as of cholesterol side-chain cleavage enzyme, thereby inhibiting the production of steroid hormones including glucocorticoids, mineralocorticoids, androgens, and estrogens. In addition, amphenone B inhibits the production of thyroxine by a thiouracil-like mechanism, specifically via inhibition of organic binding of iodine and uptake of iodide by the thyroid gland.
WBaicalein (5,6,7-trihydroxyflavone) is a flavone, a type of flavonoid, originally isolated from the roots of Scutellaria baicalensis and Scutellaria lateriflora. It is also reported in Oroxylum indicum and Thyme. It is the aglycone of baicalin. Baicalein is one of the active ingredients of Sho-Saiko-To, a Chinese herbal supplement believed to enhance liver health.
WBrilanestrant (INN) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Aragon Pharmaceuticals and was under development by Genentech for the treatment of locally advanced or metastatic estrogen receptor (ER)-positive breast cancer.
WChemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.
WClometerone (INN), or clometherone (USAN), also known as 6α-chloro-16α-methylprogesterone, is a synthetic pregnane steroid and derivative of progesterone which was reported in 1962 and is described as an antiestrogen and antiandrogen but was never marketed.
WCytestrol acetate is a steroidal antiestrogen and a cytostatic antineoplastic agent which was developed for the treatment of breast cancer but was never marketed. It is an 11α-hydroxylated derivative of ethinylestradiol in which a bis(2-chloroethyl)amine nitrogen mustard moiety has been attached as an ester at the C3 position and acetate esters have been attached at the C11α and C17β positions. The mechanism of action of cytestrol acetate in breast cancer is two-fold: (1) acting as an antiestrogen similarly to fulvestrant or ICI-164384; and (2) having cytostatic actions via the carbamate–nitrogen mustard moiety analogously to estramustine phosphate. The drug shows potent efficacy against breast cancer superior to that of tamoxifen in in vitro models.
WDanazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken by mouth.
WDimepregnen, or 6α,16α-dimethylpregn-4-en-3β-ol-20-one, is a pregnene steroid described as an antiestrogen that was synthesized in 1968 and was never marketed. It is similar in structure to the progestins and progesterone derivatives melengestrol and anagestone.
WElacestrant (INN) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Eisai and is under development by Radius Health and Takeda for the treatment estrogen receptor (ER)-positive advanced breast cancer. Elacestrant has dose-dependent, tissue-selective estrogenic and antiestrogenic activities, with biphasic weak partial agonist activity at the ER at low doses and antagonist activity at higher doses. It shows agonistic activity on bone and antagonistic activity on breast and uterine tissues. Unlike the SERD fulvestrant, elacestrant is able to readily cross the blood-brain-barrier into the central nervous system, where it can target breast cancer metastases in the brain, and is orally bioavailable and does not require intramuscular injection.
WEpitiostanol, sold under the brand name Thiodrol, is an injected antiestrogen and anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which was described in the literature in 1965 and has been marketed in Japan as an antineoplastic agent for the treatment of breast cancer since 1977.
WERX-11, also known as ERα coregulator-binding modulator-11, is a novel antiestrogen and experimental hormonal antineoplastic agent which is being researched for the potential treatment of estrogen receptor-positive breast cancer. It is not a competitive antagonist of the estrogen receptor (ER) like conventional antiestrogens such as tamoxifen or fulvestrant; instead of binding to the ligand-binding site of the ER, ERX-11 interacts with a different part of the ERα and blocks protein–protein interactions of the ERα with coregulators that are necessary for the receptor to act and regulate gene expression. It was designed to bind to the coregulator binding region of the ERα and inhibit the ERα/coactivator interaction, although its precise binding site and mode of action have yet to be fully elucidated and understood. Nonetheless, it is clear that ERX-11 binds within the AF-2 domain of the ERα.
WEtacstil is an orally active, nonsteroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer. It was shown to overcome antiestrogen resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties. Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604, of which etacstil is a prodrug. This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).
WEthamoxytriphetol is a synthetic nonsteroidal antiestrogen that was studied clinically in the late 1950s and early 1960s but was never marketed. MER-25 was first reported in 1958, and was the first antiestrogen to be discovered. It has been described as "essentially devoid of estrogenic activity" and as having "very low estrogenic activity in all species tested". However, some estrogenic effects in the uterus have been observed, so it is not a pure antiestrogen but is, instead, technically a selective estrogen receptor modulator (SERM). For all intents and purposes, it is a nearly pure antiestrogen, however.
WGestrinone, sold under the brand names Dimetrose and Nemestran among others, is a medication which is used in the treatment of endometriosis. It has also been used to treat other conditions such as uterine fibroids and heavy menstrual bleeding and has been investigated as a method of birth control. Gestrinone is used alone and is not formulated in combination with other medications. It is taken by mouth or in through the vagina.
WGlyceollin I is a glyceollin, a type of prenylated pterocarpan. It is a phytoalexin found in the soybean.
WGlyceollin III is a glyceollin, a type of pterocarpan, found in the soybean. It has an antiestrogenic effect. In soil, it has an antifungal activity against Aspergillus sojae.
WA gonadotropin-releasing hormone agonist is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatment of hormone-sensitive cancers such as prostate cancer and breast cancer, certain gynecological disorders like heavy periods and endometriosis, high testosterone levels in women, early puberty in children, as a part of transgender hormone therapy, and to delay puberty in transgender youth among other uses. GnRH agonists are given by injections into fat, as implants placed into fat, and as nasal sprays.
WGonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.
W7β-Hydroxydehydroepiandrosterone, also known as 3β,7β-dihydroxyandrost-4-ene-17-one, is an endogenous, naturally occurring steroid and a metabolite of dehydroepiandrosterone (DHEA). The major metabolic pathway of DHEA outside the liver is via 7-hydroxylation into 7α-OH-DHEA and 7β-OH-DHEA. 7β-OH-DHEA has weak antiestrogenic activity, selectively antagonizing the estrogen receptor ERβ.
W4'-Hydroxynorendoxifen is a synthetic, nonsteroidal antiestrogen of the triphenylethylene group. It is a dual selective estrogen receptor modulator (SERM) and aromatase inhibitor (AI), and was derived from tamoxifen, a SERM, and norendoxifen, a metabolite of tamoxifen that has been found to act as an AI. The drug has been suggested for potential development as a treatment for estrogen receptor (ER)-positive breast cancer. It was synthesized in 2015.
WICI-164384, also known as N-n-butyl-N-methyl-11-(3,17β-dihydroxyestra-1,3,5 -trien-7α-yl)undecanamide, is a steroidal antiestrogen and a synthetic derivative of estradiol which is closely related to fulvestrant and was never marketed. It is a silent antagonist of the estrogen receptor (ER) with no intrinsic estrogenic activity and hence is a pure antiestrogen, unlike selective estrogen receptor modulators (SERMs) like tamoxifen. The drug was under development by AstraZeneca for the treatment of breast cancer but was discontinued in favor of fulvestrant, which is very similar to ICI-164384 but is more potent in comparison.
WMepitiostane, sold under the brand name Thioderon, is an orally active antiestrogen and anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which is marketed in Japan as an antineoplastic agent for the treatment of breast cancer. It is a prodrug of epitiostanol. The drug was patented and described in 1968.
WMethylepitiostanol, known by the nicknames Epistane, Hemapolin, Havoc, and Epi Plex, is a synthetic and orally active anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which was first described in the literature in 1974 but was never marketed for medical use. It is the 17α-methylated derivative of epitiostanol, an AAS and antiestrogen which was formerly used in the treatment of breast cancer in Japan. Similarly to mepitiostane, methylepitiostanol is an orally active variant of epitiostanol. Due to its C17α methyl group, the drug is considered to have a high potential for hepatotoxicity.
WMethylpiperidinopyrazole (MPP) is a synthetic, nonsteroidal, and highly selective antagonist of ERα that is used in scientific research to study the function of this receptor. It has 200-fold selectivity for ERα over ERβ and 1000-fold selectivity for blocking ERα-mediated gene transcription relative to that of ERβ.
WMIBE is a synthetic, nonsteroidal antiestrogen that acts as a dual antagonist of the ERα and the GPER. It was found to prevent estradiol-induced proliferation of MCF-7 breast cancer cells, an action that was mediated via inhibition of both receptors. The drug was synthesized in 2012. It has been suggested that drugs like MIBE might be superior agents in the treatment of breast cancer compared to current antiestrogens like tamoxifen and fulvestrant, which are antagonistic at the ERα but were found in 2005 to be GPER agonists.
WMinamestane (INN is a steroidal aromatase inhibitor which was under development by Farmitalia-Carlo Erba as an antineoplastic agent in the mid-1990s but was never marketed.
WPHTPP is a synthetic, nonsteroidal, and highly selective antagonist of ERβ that is used in scientific research to study the function of this receptor. It possesses 36-fold selectivity for ERβ over ERα, and is a silent antagonist of ERβ.
WPlomestane is a steroidal, irreversible aromatase inhibitor which was under development by Marion Merrell Dow/Hoechst Marion Russell as an antineoplastic agent for the treatment of breast cancer. It was found to be effective in preclinical studies and was also found to produce few adverse effects in human clinical trials, significantly reducing estrogen levels with a single administration. However, development of the drug for clinical use was halted due to "technical issues" and it was never marketed.
WProchloraz, brand name Sportak, is an imidazole fungicide that was introduced in 1978 and is widely used in Europe, Australia, Asia, and South America within gardening and agriculture to control the growth of fungi. It is not registered for use in the United States. Similarly to other azole fungicides, prochloraz is an inhibitor of the enzyme lanosterol 14α-demethylase (CYP51A1), which is necessary for the production of ergosterol – an essential component of the fungal cell membrane – from lanosterol. The agent is a broad-spectrum, protective and curative fungicide, effective against Alternaria spp., Botrytis spp., Erysiphe spp., Helminthosporium spp., Fusarium spp., Pseudocerosporella spp., Pyrenophora spp., Rhynchosporium spp., and Septoria spp.
WRU-16117 is an estrogen medication which was investigated for the potential treatment of symptoms of estrogen deficiency such as hot flashes and osteoporosis in women but was never marketed. It was developed for use by mouth.
WTAS-108, also known as SR-16234, is a drug discovered by Masato Tanabe and under development by SRI International and Taiho Pharmaceutical. It is a steroid hormone that has shown signs of treating and preventing breast cancer, even in patients where tamoxifen has failed.
W(R,R)-Tetrahydrochrysene is a drug used to study the estrogen receptors (ERs) in scientific research. It is an ERβ antagonist and an ERα agonist with 10-fold higher affinity for ERβ relative to ERα. (R,R)-THC is a silent antagonist of ERβ, and, uniquely relative to other known ERβ antagonists, a passive antagonist of the receptor.
WTrilostane, sold under the brand names Modrenal and Vetoryl among others, is a medication which has been used in the treatment of Cushing's syndrome, Conn's syndrome, and postmenopausal breast cancer in humans. It was withdrawn for use in humans in the United States in the 1990s but was subsequently approved for use in veterinary medicine in the 2000s to treat Cushing's syndrome in dogs. It is taken by mouth.