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Trade names | Aipuliete, Chuanliu |
Other names | ONO-9302; SKF-105657; 17β-(tert-Butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid |
Routes of administration | By mouth [1] |
Drug class | 5α-Reductase inhibitor |
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Pharmacokinetic data | |
Bioavailability | 93% [2] |
Elimination half-life | 26 hours [2] |
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Chemical and physical data | |
Formula | C25H37NO3 |
Molar mass | 399.575 g·mol−1 |
3D model (JSmol) | |
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Epristeride, sold under the brand names Aipuliete and Chuanliu, is a medication which is used in the treatment of enlarged prostate in China. [3] [4] [5] It is taken by mouth. [1]
Epristeride is a 5α-reductase inhibitor and works by decreasing the production of dihydrotestosterone (DHT), an androgen sex hormone, in certain parts of the body like the prostate gland. [6] [7] [8] It inhibits two of the three forms of 5α-reductase but is of relatively low efficacy and can decrease DHT levels in the blood only by about 25 to 54%. [8]
Epristeride was under development for the treatment of enlarged prostate, scalp hair loss, and acne in the United States and other countries in the 1990s but did not complete development in these countries. [6] [4] Instead, it was developed and introduced for the treatment of enlarged prostate in China in 2000. [4]
Epristeride is used in the treatment of benign prostatic hyperplasia (BPH), otherwise known as enlarged prostate. [3] [4]
Epristeride is a selective, transition-state, non-competitive or uncompetitive, irreversible inhibitor of 5α-reductase, [6] [7] and is specific to the type II isoform of the enzyme similarly to finasteride and turosteride but unlike dutasteride. [8]
Epristeride is unique in its mechanism of action relative to finasteride and dutasteride in that it binds irreversibly to 5α-reductase and results in the formation of an unproductive complex of the 5α-reductase enzyme, the substrate testosterone, and the cofactor NADPH. [8] [9] For this reason, testosterone is caught in a trap, and it was initially speculated that the reciprocal increase in intraprostatic levels of testosterone seen with finasteride and dutasteride should not happen with epristeride. [8] [9] However, subsequent clinical data have not supported this hypothesis. [8] Moreover, in spite of the fact that epristeride is a very potent inhibitor of 5α-reductase type II (0.18–2 nM), it has been found to reduce circulating levels of dihydrotestosterone (DHT) by only 25 to 54% following 8 days of therapy over a dosage range of 0.4 to 160 mg/day. [8] For this reason, relative to other 5α-reductase inhibitors like finasteride and dutasteride, the degree of DHT suppression with epristeride falls short of that desirable for full clinical benefit. [8]
The oral bioavailability of epristeride is 93%. [2] It has an elimination half-life of 26 hours. [2]
Epristeride, also known as 17β-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid, is a synthetic androstane steroid.
Epristeride was under development for the treatment of BPH, androgenic alopecia (pattern hair loss), and acne vulgaris by SmithKline Beecham (now GlaxoSmithKline) in the 1990s and reached phase III clinical trials in the United States, United Kingdom, and Japan, [6] but ultimately was never marketed in these countries. [4] Instead, epristeride was developed by Ono Pharmaceutical and introduced for the treatment of BPH in China in 2000. [4]
Epristeride is the generic name of the drug and its INN, USAN, BAN, and JAN. [5]
Epristeride is marketed under the brand names Aipuliete and Chuanliu in China. [5] [4]
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 of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
Dihydrotestosterone is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain. This enzyme mediates reduction of the C4-5 double bond of testosterone. Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR).
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia in men. It can also be used to treat excessive hair growth in women and as a part of hormone therapy for transgender women. It is taken by mouth.
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 of 5α-reductase encoded by the genes SRD5A1, SRD5A2, and SRD5A3.
5α-Reductase inhibitors (5-ARIs), also known as dihydrotestosterone (DHT) blockers, are a class of medications with antiandrogenic effects which are used primarily in the treatment of enlarged prostate and scalp hair loss. They are also sometimes used to treat excess hair growth in women and as a component of hormone therapy for transgender women.
Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of an enlarged prostate. A few months may be required before benefits occur. It is also used for scalp hair loss in men and as a part of hormone therapy in transgender women. It is taken orally.
Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a kidney stone is better when the stone is larger. It is taken by mouth.
Allylestrenol, sold under the brand names Gestanin and Turinal among others, is a progestin medication which is used to treat recurrent and threatened miscarriage and to prevent premature labor in pregnant women. However, except in the case of proven progesterone deficiency, its use for such purposes is no longer recommended. It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men. The medication is used alone and is not formulated in combination with an estrogen. It is taken by mouth.
Turosteride (FCE-26,073) is a selective inhibitor of the enzyme 5α-reductase which was under investigation by GlaxoSmithKline for the treatment of benign prostatic hyperplasia (BPH), but was never marketed. Similarly to finasteride, turosteride is selective for the type II isoform of 5α-redcutase, with about 15-fold selectivity for it over type I isoform of the enzyme. In animal studies it has been shown to inhibit prostate size and retard tumor growth. It may also be useful for the treatment of acne and hair loss.
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.
BOMT, also known by its developmental code name Ro 7-2340 and as 6α-bromo-4-oxa-17α-methyl-5α-dihydrotestosterone, is a synthetic steroidal antiandrogen which was first developed in 1970 and was never marketed for medical use. It is the 6α-brominated, 4-oxygenated, and 17α-methylated derivative of the androgen dihydrotestosterone (DHT). Along with benorterone, cyproterone, and flutamide, BOMT was among the earliest antiandrogens to be developed and extensively studied, although it is less well-documented in comparison to the others. BOMT has been investigated clinically in the treatment of benign prostatic hyperplasia, though development for this use did not continue. There was also interest in BOMT for the potential applications of acne, pattern hair loss, and possibly prostate cancer, but it was not developed for these indications either.
A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.
5α-Dihydronandrolone is a naturally occurring anabolic–androgenic steroid (AAS) and a 5α-reduced derivative of nandrolone (19-nortestosterone). It is a major metabolite of nandrolone and is formed from it by the actions of the enzyme 5α-reductase analogously to the formation of dihydrotestosterone (DHT) from testosterone.
Androstanolone, or stanolone, also known as dihydrotestosterone (DHT) and sold under the brand name Andractim among others, is an androgen and anabolic steroid (AAS) medication and hormone which is used mainly in the treatment of low testosterone levels in men. It is also used to treat breast development and small penis in males. It is typically given as a gel for application to the skin, but can also be used as an ester by injection into muscle.
MK-386, also known as 4,7β-dimethyl-4-aza-5α-cholestan-3-one, is a synthetic, steroidal 5α-reductase inhibitor which was first reported in 1994 and was never marketed. It is a 4-azasteroid and a potent and selective inhibitor of 5α-reductase type I and shows high selectivity for inhibition of human 5α-reductase type I over 5α-reductase type II, with IC50 values of 0.9 nM and 154 nM, respectively. The drug was under investigation for potential treatment of androgen-dependent conditions such as acne and pattern hair loss (androgenic alopecia or baldness), but was discontinued in early clinical trials due to observations of hepatotoxicity such as elevated liver enzymes.
This article is about the discovery and development of 5α-reductase inhibitors (5-ARIs), also known as dihydrotestosterone (DHT) blockers.
MK-434 is a 5α-reductase inhibitor which was under development in the 1990s by Merck & Co for the treatment of a variety of androgen-dependent conditions including benign prostatic hyperplasia, prostate cancer, pattern hair loss, excessive hair growth, acne, and seborrhea but was never marketed. It acts as a selective inhibitor of 5α-reductase type 2. The drug has been found to decrease circulating dihydrotestosterone levels by a maximum of approximately 50% in men. MK-434 is a synthetic 4-azasteroid and is structurally related to other 5α-reductase inhibitors like finasteride.