ATC Group: L02B Hormone antagonists and related agents

Abarelix is a synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. Abarelix is primarily used in oncology to reduce the amount of testosterone made in patients with advanced symptomatic prostate cancer for which no other treatment options are available.

Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. Specifically, abiraterone selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and prostatic tumour tissues. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals.

Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. It inhibits the enzyme aromatase, which is responsible for converting androgens to estrogens. Anastrozole is a drug indicated in the treatment of breast cancer in post-menopausal women.

Apalutamide is an orally administered, selective Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide treatment decreases tumor cell proliferation and increases apoptosis leading to potent antitumor activity.

Bicalutamide is a non-steroidal antiandrogen, devoid of other endocrine activity. It binds to androgen receptors without activating gene expression, and thus inhibits the androgen stimulus. Regression of prostatic tumours results from this inhibition.

Darolutamide is an androgen receptor (AR) inhibitor with a flexible polar-substituted pyrazole structure that binds with high affinity directly to the receptor ligand binding domain. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. Darolutamide treatment decreases prostate tumour cell proliferation leading to potent antitumour activity.

Degarelix is a selective gonadotrophin releasing-hormone (GnRH) antagonist that competitively and reversibly binds to the pituitary GnRH receptors, thereby rapidly reducing the release of the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and thereby reducing the secretion of testosterone (T) by the testes.

Elacestrant, a tetrahydronaphthalene compound, is a potent, selective and orally active estrogen receptor-α (ERα) antagonist and degrader. Elacestrant inhibits the estradiol-dependent and independent growth of ERα-positive breast cancer cells, including models harbouring estrogen receptor 1 (ESR1) gene mutations.

Enzalutamide is a potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. Enzalutamide treatment decreases the growth of prostate cancer cells and can induce cancer cell death and tumour regression.

Exemestane is an irreversible, steroidal aromatase inhibitor, structurally related to the natural substrate androstenedione.

Flutamide is a non-steroidal, highly specific, orally active anti-androgenic agent. The pharmacologically active metabolite, hydroxyflutamide, is believed to exert an anti-androgenic effect directly on the target tissues, either by inhibiting androgen uptake or by blocking cytoplasmic and nuclear binding of androgen. Flutamide is indicated for the treatment of advanced prostatic carcinoma in which suppression of testosterone effects is indicated.

Fulvestrant is a competitive estrogen receptor (ER) antagonist with an affinity comparable to estradiol. Fulvestrant blocks the trophic actions of estrogens without any partial agonist (estrogen-like) activity.

Letrozole is a non-steroidal aromatase inhibitor. It inhibits the aromatase enzyme by competitively binding to the haem of the aromatase cytochrome P450, resulting in a reduction of oestrogen biosynthesis in all tissues where present.

Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to GnRH receptors in the anterior pituitary gland preventing native GnRH from binding and signalling the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Consequently, the production of testosterone from the testes is reduced.

Tamoxifen is a non-steroidal, triphenylethylene-based drug which displays a complex spectrum of oestrogen antagonist and oestrogen agonist-like pharmacological effects in different tissues.

Toremifene is a nonsteroidal triphenylethylene derivative that binds to estrogen receptors and may produce estrogenic, anti-estrogenic or both effects, depending upon the duration of treatment, animal species, gender, target organ and variable selected. Toremifene is indicated in first line hormone treatment of hormone-dependent metastatic breast cancer in postmenopausal patients.