Clinical data | |
---|---|
Trade names | Lentaron, others |
Other names | 4-Hydroxyandrost-4-ene-3,17-dione |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Intramuscular injection |
Drug class | Aromatase inhibitor; Antiestrogen |
ATC code | |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.153.838 |
Chemical and physical data | |
Formula | C19H26O3 |
Molar mass | 302.414 g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
Formestane, formerly sold under the brand name Lentaron among others, is a steroidal, selective aromatase inhibitor which is used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. [1] The drug is not active orally, and was available only as an intramuscular depot injection. Formestane was not approved by the United States FDA and the injectable form that was used in Europe in the past has been withdrawn from the market. [2] Formestane is an analogue of androstenedione.
Formestane is often used to suppress the production of estrogens from anabolic steroids or prohormones. It also acts as a prohormone to 4-hydroxytestosterone, an active steroid which displays weak androgenic activity in addition to acting as a weak aromatase inhibitor.
Generation | Medication | Dosage | % inhibitiona | Classb | IC50c |
---|---|---|---|---|---|
First | Testolactone | 250 mg 4x/day p.o. | ? | Type I | ? |
100 mg 3x/week i.m. | ? | ||||
Rogletimide | 200 mg 2x/day p.o. 400 mg 2x/day p.o. 800 mg 2x/day p.o. | 50.6% 63.5% 73.8% | Type II | ? | |
Aminoglutethimide | 250 mg mg 4x/day p.o. | 90.6% | Type II | 4,500 nM | |
Second | Formestane | 125 mg 1x/day p.o. 125 mg 2x/day p.o. 250 mg 1x/day p.o. | 72.3% 70.0% 57.3% | Type I | 30 nM |
250 mg 1x/2 weeks i.m. 500 mg 1x/2 weeks i.m. 500 mg 1x/1 week i.m. | 84.8% 91.9% 92.5% | ||||
Fadrozole | 1 mg 1x/day p.o. 2 mg 2x/day p.o. | 82.4% 92.6% | Type II | ? | |
Third | Exemestane | 25 mg 1x/day p.o. | 97.9% | Type I | 15 nM |
Anastrozole | 1 mg 1x/day p.o. 10 mg 1x/day p.o. | 96.7–97.3% 98.1% | Type II | 10 nM | |
Letrozole | 0.5 mg 1x/day p.o. 2.5 mg 1x/day p.o. | 98.4% 98.9%–>99.1% | Type II | 2.5 nM | |
Footnotes:a = In postmenopausal women. b = Type I: Steroidal, irreversible (substrate-binding site). Type II: Nonsteroidal, reversible (binding to and interference with the cytochrome P450 heme moiety). c = In breast cancer homogenates. Sources: See template. |
Anastrozole, sold under the brand name Arimidex among others, is an antiestrogenic 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.
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.
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).
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.
Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated or used in combination with other medications. It is taken by mouth.
Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.
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.
Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate.
Antihormone therapy is a type of hormone therapy that suppresses selected hormones or their effects, in contrast with hormone replacement therapy, which encourages hormone activity.
A hormone-receptor-positive (HR+) tumor is a tumor which consists of cells that express receptors for certain hormones. The term most commonly refers to estrogen receptor positive tumors, but can also include progesterone receptor positive tumors. Estrogen-receptor-positive tumors depend on the presence of estrogen for ongoing proliferation.
Fadrozole, sold under the brand name Afema, is a selective, nonsteroidal aromatase inhibitor which is or has been used in Japan for the treatment of breast cancer.
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 selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the estrogen receptor (ER) and, in the process of doing so, causes the ER to be degraded and thus downregulated. They are used to treat estrogen receptor-sensitive or progesterone receptor-sensitive breast cancer, along with older classes of drugs like selective estrogen receptor modulators (SERMs) and aromatase inhibitors.
Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer. It is taken by mouth.
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.
Endocrine therapy is a common treatment for estrogen receptor positive breast cancer. However, resistance to this therapy can develop, leading to relapse and progression of disease. This highlights the need for new strategies to combat this resistance.