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A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...
which
inhibit Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotr ...
s one or more of the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s that are involved in the process of steroidogenesis, the
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...
of
endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s and
steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
s. They may inhibit the production of
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
and other
sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...
s,
sex steroid Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s such as
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s,
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s, and
progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the bod ...
s,
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...
s such as glucocorticoids and
mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
s, and
neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was co ...
s. They are used in the treatment of a variety of
medical condition A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s that depend on endogenous steroids. Steroidogenesis inhibitors are analogous in effect and use to antigonadotropins (which specifically inhibit gonadal sex steroid production), but work via a different
mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...
; whereas antigonadotropins suppress gonadal production of sex steroids by effecting
negative feedback Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...
on and thereby suppressing the hypothalamic–pituitary–gonadal axis, steroidogenesis inhibitors directly inhibit the enzymatic biosynthesis of steroids.


Types, examples, and uses


Cholesterol synthesis inhibitors


Acetyl-CoA to lanosterol inhibitors

* HMG-CoA reductase (HMGCR) inhibitors, also known as statins, prevent the conversion of into
mevalonic acid Mevalonic acid (MVA) is a key organic compound in biochemistry; the name is a contraction of dihydroxymethylvalerolactone. The carboxylate anion of mevalonic acid, which is the predominant form in biological environments, is known as ''mevalonat ...
, a relatively early step in the biosynthesis of cholesterol from
acetyl coenzyme A Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
(acetyl-CoA), and thereby decrease cholesterol levels. Examples of statins include
atorvastatin Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth. Common ...
, lovastatin,
rosuvastatin Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, ...
, and
simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of hear ...
. They are used in the treatment of
hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...
for the purpose of lowering the risk of
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
-related
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
. *
Farnesyl pyrophosphate synthase Dimethylallyltranstransferase (DMATT), also known as farnesylpyrophosphate synthase (FPPS) or as farnesyldiphosphate synthase (FDPS), is an enzyme that in humans is encoded by the FDPS gene and catalyzes the transformation of dimethylallylpyr ...
(FPPS) inhibitors prevent the conversion of
isopentenyl pyrophosphate Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of i ...
(IPP) into
farnesyl pyrophosphate Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport c ...
(FPP), a mid-range step in the biosynthesis of cholesterol from acetyl-CoA, and thereby inhibit cholesterol production. They notably do not significantly lower ''circulating'' levels of cholesterol however, and hence, unlike statins, are not suitable for the treatment of hypercholesterolemia. The main examples of FPPS inhibitors are nitrogenous
bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
s such as alendronate, ibandronate, pamidronate, risedronate, and zoledronate, which are used in the treatment of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...
. * Other early-stage cholesterol synthesis inhibitors like colestolone.


Lanosterol to cholesterol inhibitors

* 7-Dehydrocholesterol reductase (7-DHCR) inhibitors such as AY-9944 and BM-15766 inhibit the production of cholesterol from 7-dehydrocholesterol, one of the last steps in cholesterol biosynthesis. Loss-of-function mutations in the
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
encoding 7-DHCR result in Smith–Lemli–Opitz syndrome (SLOS) and dramatic accumulation of 7-dehydrocholesterol. 7-DHCR inhibitors produce an acquired form of SLOS in animals, and as such, like 24-DHCR inhibitors (see below), are probably too
toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a sub ...
to be used clinically. * 24-Dehydrocholesterol reductase (24-DHCR) inhibitors such as azacosterol and triparanol inhibit the production of cholesterol from desmosterol, one of the last steps in cholesterol biosynthesis, and were formerly used to treat hypercholesterolemia, but were withdrawn from the market due to toxicity caused by accumulation of desmosterol in tissues.


Steroid hormone synthesis inhibitors


Non-specific steroid hormone synthesis inhibitors

* Cholesterol side-chain cleavage enzyme (P450scc, CYP11A1) inhibitors such as
aminoglutethimide 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. ...
,
ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
, and
mitotane Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. It is a derivative of the early insecticide ...
inhibit the production of
pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocor ...
from cholesterol and thereby prevent the synthesis of all steroid hormones. They have been used to inhibit
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...
synthesis in the treatment of
Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a ...
and adrenocortical carcinoma, and ketoconazole has also been used to inhibit androgen production in the treatment of
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...
. * 3β-Hydroxysteroid dehydrogenase (3β-HSD) inhibitors such as
amphenone B Amphenone 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 cort ...
, azastene, cyanoketone, epostane,
mitotane Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. It is a derivative of the early insecticide ...
, and trilostane inhibit the conversion of Δ5-3β- hydroxysteroids into Δ4-3-
ketosteroid 150px, Androstenedione 150px, Androsterone 150px, Estrone A ketosteroid, or an oxosteroid, is a steroid in which a hydrogen atom has been replaced with a ketone (C=O) group. A 17-ketosteroid is a ketosteroid in which the ketone is located ...
s and thereby inhibit the production of most of the steroid hormones. Due to inhibition of
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the majo ...
biosynthesis, they have been investigated as
contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
s and
abortifacient An abortifacient ("that which will cause a miscarriage" from Latin: '' abortus'' "miscarriage" and '' faciens'' "making") is a substance that induces abortion. This is a nonspecific term which may refer to any number of substances or medications, ...
s (though ultimately have never been marketed for this indication), and trilostane was formerly used to inhibit corticosteroid synthesis in the treatment of Cushing's syndrome. * 17α-Hydroxylase/17,20-lyase (CYP17A1) inhibitors such as
abiraterone acetate Abiraterone 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 metastasis, metastatic Prostate cancer#Castration-resistant cancer, ca ...
,
etomidate Etomidate (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardiove ...
,
galeterone Galeterone (developmental code names TOK-001, VN/124-1) is a steroidal antiandrogen which was under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique triple mechanism of action, acting as an androgen ...
,
ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
, and
orteronel Orteronel (TAK-700) is a nonsteroidal CYP17A1 inhibitor that was being developed for the treatment of cancer by Takeda Pharmaceutical Company in conjunction with Millennium Pharmaceuticals. It completed two phase III clinical trials for metastati ...
inhibit the production of androgens and glucocorticoids and are used to reduce androgen levels in the treatment of prostate cancer. Selective 17,20-lyase inhibitors such as
seviteronel __NOTOC__ Seviteronel (developmental codes VT-464 and, formerly, INO-464) is an experimental cancer medication which is under development by Viamet Pharmaceuticals and Innocrin Pharmaceuticals for the treatment of prostate cancer and breast canc ...
inhibit only androgen production without affecting glucocorticoid synthesis and are under development for the treatment of prostate cancer.


Corticosteroid-specific synthesis inhibitors

*
21-Hydroxylase Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...
(CYP21A2) inhibitors prevent the production of corticosteroids from
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the majo ...
and
17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many o ...
. * 11β-Hydroxylase (CYP11B1) inhibitors such as
amphenone B Amphenone 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 cort ...
,
etomidate Etomidate (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardiove ...
,
ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
, metyrapone,
mitotane Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. It is a derivative of the early insecticide ...
, and osilodrostat inhibit the production of the potent corticosteroids
cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal g ...
,
corticosterone Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...
, and
aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
from the less potent corticosteroids
11-deoxycorticosterone 11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone (INN), deoxycortone, and cortexone, is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid ...
and 11-deoxycortisol and are used in the diagnosis and treatment of Cushing's syndrome. * Aldosterone synthase (CYP11B2) inhibitors such as metyrapone,
mitotane Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. It is a derivative of the early insecticide ...
, and osilodrostat prevent the production of the potent mineralocorticoid aldosterone from the less potent mineralocorticoid corticosterone. Osilodrostat was investigated for the treatment of
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
,
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
, and renal disease, but development for these indications was discontinued.


Sex steroid-specific synthesis inhibitors

* 17β-Hydroxysteroid dehydrogenase (17β-HSD) inhibitors prevent the reversible conversion of the weak androgens dehydroepiandrosterone (DHEA) and
4-androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
into the more potent androgen
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
and the weak estrogen
estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...
into the more potent estrogen
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...
. *
5α-Reductase inhibitor 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes o ...
s (5-ARIs) such as
finasteride Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women and as a part of h ...
, dutasteride, epristeride, and alfatradiol prevent the conversion of
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
into the more potent androgen
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
(DHT) and are used in the treatment of
benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
(BPH) and
androgenic alopecia Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...
(pattern hair loss). These drugs also inhibit the formation of neurosteroids such as
allopregnanolone Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum ...
,
tetrahydrodeoxycorticosterone Tetrahydrodeoxycorticosterone (abbreviated as THDOC; 3α,21-dihydroxy-5α-pregnan-20-one), also referred to as ''allotetrahydrocorticosterone'', is an endogenous neurosteroid. It is synthesized from the adrenal hormone deoxycorticosterone by the ...
(THDOC), and 3α-androstanediol from progesterone, 11-deoxycorticosterone, and DHT, respectively, which may contribute to
side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s such as depression and
sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...
. * Aromatase inhibitors (AIs) such as
aminoglutethimide 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. ...
, anastrozole, exemestane, letrozole, and
testolactone Testolactone (, ) (brand name Teslac) is a non-selective, irreversible, steroidal aromatase inhibitor which is used as an antineoplastic drug to treat advanced-stage breast cancer.
inhibit the production of estrogens from androgens and are used mainly in the treatment of estrogen receptor-positive
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
. * Steroid sulfotransferase (SST) inhibitors prevent the conversion of steroid hormones such as estrone and DHEA into hormonally inactive steroid
sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
s. Although hormonally inactive, some steroid sulfates, such as
pregnenolone sulfate Pregnenolone sulfate (PS, PREGS) is an endogenous excitatory neurosteroid that is synthesized from pregnenolone. It is known to have cognitive and memory-enhancing, antidepressant, anxiogenic, and proconvulsant effects. Biological activity Pr ...
and
DHEA sulfate Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepi ...
, are important
neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was co ...
s. *
Steroid sulfatase Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a sulfatase enzyme involved in the metabolism of steroids. It is encoded by the ''STS'' gene. Reactions This enzyme catalyses the following chemi ...
(STS) inhibitors such as estradiol sulfamate, estrone sulfamate, irosustat, and danazol inhibit the conversion of steroid sulfates such as estrone sulfate and
DHEA sulfate Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepi ...
into their hormonally active forms. They have potential applications in the treatment of
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
and
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, fa ...
, and are currently under investigation for such indications.


Other steroid synthesis inhibitors

*
Lanosterol 14α-demethylase Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of ...
(CYP51A1) inhibitors such as
clotrimazole Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock ...
,
fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...
,
itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mo ...
,
ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
, miconazole, and
voriconazole Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ' ...
prevent the production of
ergosterol Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, t ...
from
lanosterol Lanosterol is a tetracyclic triterpenoid and is the compound from which all animal and fungal steroids are derived. By contrast plant steroids are produced via cycloartenol. Role in biosynthesis of other steroids Elaboration of lanosterol under en ...
. Ergosterol is absent in animals but is an essential component of the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s of many
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
and
protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
, and so lanosterol 14α-demethylase inhibitors are used as
antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...
s and
antiprotozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection. A paraphyletic group, protozoans have little in common with each other. For example, ''Entamoeba histolytica'', a unikont eukar ...
s in the treatment of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
s.


List of steroid metabolism modulators


See also

* Steroidogenic enzyme *
Neurosteroidogenesis inhibitor A neurosteroidogenesis inhibitor is a drug that inhibits the production of endogenous neurosteroids. Neurosteroids include the excitatory neurosteroids pregnenolone sulfate, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHE ...


References


External links

* {{Enzyme inhibition