Glutethimide is a hypnotic sedative that was introduced by Ciba in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similar withdrawal symptoms. Doriden was the brand-name version. Current production levels in the United States point to its use only in small-scale research. Manufacturing of the drug was discontinued in the US in 1993 and discontinued in several eastern European countries in 2006.
Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast cancer in those at high risk. It is taken by mouth.
An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include:
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome. Tamoxifen is typically taken daily by mouth for five years for breast cancer.
Aromatase, also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into estrogens. The enzyme aromatase can be found in many tissues including gonads, brain, adipose tissue, placenta, blood vessels, skin, and bone, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer. It is an important factor in sexual development.
Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exogenously. They may also be used for chemoprevention in women at high risk for breast cancer.
Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer.
Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. It has also been used by bodybuilders, athletes, and other men for muscle-building and performance- and physique-enhancing purposes. AG is taken by mouth three or four times per day.
Exemestane, sold under the brand name Aromasin among others, is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.
Methylpentynol is a tertiary hexynol with hypnotic/sedative and anticonvulsant effects and an exceptionally low therapeutic index. It was discovered by Bayer in 1913 and was used shortly thereafter for the treatment of insomnia, but its use was quickly phased out in response to newer drugs with far more favorable safety profiles.
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production. Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens. Antiestrogens are commonly used to stop steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels. Decreased levels of estrogen can lead to complications in sexual development. Antiandrogens are sex hormone antagonists which are able to lower the production and the effects that testosterone can have on female bodies.
Testolactone is a non-selective, irreversible, steroidal aromatase inhibitor which is used as an antineoplastic drug to treat advanced-stage breast cancer. The drug was discontinued in 2008 and is no longer available for medical use.
Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.
Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.
Steroidal aromatase inhibitors are a class of drugs that are mostly used for treating breast cancer in postmenopausal women. High levels of estrogen in breast tissue increases the risk of developing breast cancer and the enzyme aromatase is considered to be a good therapeutic target when treating breast cancer due to it being involved in the final step of estrogen biosynthetic pathway and also its inhibition will not affect production of other steroids. Aromatase Inhibitors are classified into two categories based on their structure, nonsteroidal and steroidal; the latter resemble the structure of androstenedione. Steroidal aromatase inhibitors irreversibly inhibit the enzyme by binding covalently to the binding site of aromatase so the substrate cannot access it.
A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of the enzymes that are involved in the process of steroidogenesis, the biosynthesis of endogenous steroids and steroid hormones. They may inhibit the production of cholesterol and other sterols, sex steroids such as androgens, estrogens, and progestogens, corticosteroids such as glucocorticoids and mineralocorticoids, and neurosteroids. They are used in the treatment of a variety of medical conditions that depend on endogenous steroids.
Norendoxifen, also known as 4-hydroxy-N,N-didesmethyltamoxifen, is a nonsteroidal aromatase inhibitor (AI) of the triphenylethylene group that was never marketed. It is an active metabolite of the selective estrogen receptor modulator (SERM) tamoxifen. Unlike tamoxifen, norendoxifen is not a SERM, and instead has been found to act as a potent and selective competitive inhibitor of aromatase (Ki = 35 nM). Drugs with dual SERM and AI activity, such as 4'-hydroxynorendoxifen, have been developed from norendoxifen, and may have therapeutic potential as antiestrogens in the treatment of estrogen receptor-positive breast cancer.
4'-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.
Irosustat is an orally active, irreversible, nonsteroidal inhibitor of steroid sulfatase (STS) and member of the aryl sulfamate ester class of drugs that was under development by Sterix Ltd and Ipsen for the treatment of hormone-sensitive cancers such as breast cancer, prostate cancer, and endometrial cancer but has not yet been marketed. The drug was first designed and synthesized in the group of Professor Barry V L Potter at the Department of Pharmacy & Pharmacology, University of Bath, working together with Professor Michael J. Reed at Imperial College, London and its initial development was undertaken through the university spin-out company Sterix Ltd and overseen by Cancer Research UK (CRUK). Results of the "first-in-class" clinical trial in breast cancer of an STS inhibitor in humans were published in 2006 and dose optimisation studies and further clinical data have been reported.
Non-Steroidal Aromatase Inhibitors (NSAIs) are one of two categories of aromatase inhibitors (AIs). AIs are divided into two categories, steroidal aromatase inhibitors and non-steroidal aromatase inhibitors that is based on their mechanism of action and structure. NSAIs are mainly used to treat breast cancer in women. NSAIs binding is a reversible process where NSAIs binds to the aromatase enzyme through non-covalent interactions. When aromatase inhibitors (AIs) are used to treat breast cancer the main target is the aromatase enzyme which is responsible for the high estrogen level.
