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CYP17A1 Inhibitors
A CYP17A1 inhibitor is a type of drug that enzyme inhibitor, inhibits the enzyme CYP17A1. CYP17A1 inhibitors work by blocking specific enzyme functions, impacting androgen biosynthesis. Mechanism of action CYP17A1 inhibitors may inhibit one or both of the enzyme’s functions: 17α-hydroxylase and 17,20-lyase. Some inhibitors are selective and target only the 17,20-lyase function, while others inhibit both functions. By inhibiting these enzymatic functions, CYP17A1 inhibitors prevent the conversion of pregnane steroids into androgens like testosterone. This action classifies them as androgen biosynthesis inhibitors and functional antiandrogens. Examples Examples of CYP17A1 inhibitors include the older drug ketoconazole and the newer drugs abiraterone acetate, orteronel, galeterone, and seviteronel. Clinical uses CYP17A1 inhibitors, such as abiraterone acetate, are primarily used in the treatment of prostate cancer. These drugs reduce androgen levels, which helps to slow ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth. Common side effects include tiredness, vomiting, headache, joint pain, high blood pressure, swelling, low blood potassium, high blood sugar, hot flashes, diarrhea, and cough. Other severe side effects may include liver failure and adrenocortical insufficiency. In males whose partners can become pregnant, birth control is recommended. Supplied as abiraterone acetate it is converted in the body to abiraterone. Abiraterone acetate works by suppressing the production of androgens – specifically it inhibits CYP17A1 – and thereb ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve as enzyme substrate (chemistry), substrates, with conversion by the living organism either into simpler or more complex Product (chemistry), products. Examples of biosynthetic pathways include those for the production of amino acids, lipid membrane components, and nucleotides, but also for the production of all classes of biological macromolecules, and of acetyl-coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide and other key intermediate and transactional molecules needed for metabolism. Thus, in biosynthesis, any of an array of Chemical compound, compounds, from simple to complex, are converted into other compounds, and so it includes both the catabolism and anabolism (building up and breaking down) of comple ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steroidogenesis Inhibitor
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. 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; whereas antigonadotropins suppress gonadal production of sex steroids by effecting negative feedback on and thereby suppressing the hypothalamic–pituitary–gonadal axis, steroidogenesis inhibitors directly inhibit the enzymatic biosy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steroidogenic Enzyme
__NOTOC__ Steroidogenic enzymes are enzymes that are involved in steroidogenesis and steroid biosynthesis. They are responsible for the biosynthesis of the steroid hormones, including sex steroids (androgens, estrogens, and progestogens) and corticosteroids (glucocorticoids and mineralocorticoids), as well as neurosteroids, from cholesterol. Steroidogenic enzymes are most highly expressed in classical steroidogenic tissues, such as the testis, ovary, and adrenal cortex, but are also present in other tissues in the body. List of steroidogenic enzymes * Steroid desmolases ** Cholesterol side-chain cleavage enzyme (20,22-desmolase) – steroid synthesis ** 17,20-Lyase (17,20-desmolase) – androgen synthesis * Steroid hydroxylases ** 11β-Hydroxylase – corticosteroid synthesis ** 17α-Hydroxylase – androgen and glucocorticoid synthesis ** 18-Hydroxylase (aldosterone synthase) – mineralocorticoid synthesis ** 21-Hydroxylase – corticosteroid synthesis ** Cytochrom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in an adrenal gland. In other tissues, it is produced in lower quantities. By a Circadian rhythm, diurnal cycle, cortisol is released and increases in response to Stress (biology), stress and a low Blood sugar, blood-glucose concentration. It functions to increase blood sugar through gluconeogenesis, suppress the immune system, and aid in the metabolism of calories. It also decreases bone formation. These stated functions are carried out by cortisol binding to glucocorticoid or mineralocorticoid receptors inside a cell, which then bind to DNA to affect gene expression. Health effects Metabolic response Metabolism of glucose Cortisol plays a crucial role in regulating glucose metabolism and promotes gluconeogenesis (glucose synthes ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mineralocorticoid Excess
Hyperaldosteronism is a medical condition wherein too much aldosterone is produced. High aldosterone levels can lead to lowered levels of potassium in the blood ( hypokalemia) and increased hydrogen ion excretion ( alkalosis). Aldosterone is normally produced in the adrenal glands. Primary aldosteronism is when the adrenal glands are too active and produce excess amounts of aldosterone. Secondary aldosteronism is when another abnormality causes the excess production of aldosterone. Signs and symptoms Hyperaldosteronism can be asymptomatic, but these symptoms may be present: * Fatigue * Headache * High blood pressure * Hypokalemia * Hypernatraemia * Hypomagnesemia * Intermittent or temporary paralysis * Muscle spasms * Muscle weakness * Numbness * Polyuria * Polydipsia * Tingling * Metabolic alkalosis Causes Primary Primary aldosteronism (hyporeninemic hyperaldosteronism) is most often caused by bilateral idiopathic (micronodular) adrenal hyperplasia (almost 70% of ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adrenal Insufficiency
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes (in mild cases) to organ failure and shock (in severe cases). Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow. Adrenal insufficiency can be caused by dysfunction of the adrenal gland itself, wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prednisone
Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids. It is taken Oral administration, by mouth. Common side effects may include cataracts, Osteoporosis, bone loss, easy bruising, muscle weakness, and oral candidiasis, thrush. Other side effects include weight gain, swelling, high blood sugar, increased risk of infection, and psychosis. It is generally considered safe in pregnancy and low doses appear to be safe while the user is breastfeeding. After prolonged use, prednisone must be stopped gradually. Prednisone is a prodrug and must be converted to prednisolone by the liver before it becomes active. Prednisolone then binds to glucocorticoid receptors, activating them and triggering changes in gene expression. Prednison ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau of "glucose", "cortex", and "steroid" and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure (see structure below). Glucocorticoids are part of the feedback mechanism in the immune system, which reduces certain aspects of immune function, such as inflammation. They are therefore used in medicine to treat diseases caused by an Autoimmunity, overactive immune system, such as Allergy, allergies, asthma, autoimmune diseases, and sepsis. Glucocorticoids have many Side effect, diverse effects such as pleiotropy (drugs), pleiotropy, including Adverse drug reaction, potentially harmful side effects. They also interfer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 cancer. It is a nonsteroidal CYP17A1 inhibitor and works by inhibiting the production of androgens and estrogens in the body. As of July 2017, seviteronel is in phase II clinical trials for both prostate cancer and breast cancer. In January 2016, it was designated fast-track status by the United States Food and Drug Administration for prostate cancer. In April 2017, seviteronel received fast-track designation for breast cancer as well. __TOC__ Pharmacology Pharmacodynamics Seviteronel is a nonsteroidal antiandrogen, acting specifically as an androgen synthesis inhibitor via inhibition of the enzyme CYP17A1, for the treatment of castration-resistant prostate cancer. It has approximately 10-fold selectivity for the inhibition of 17, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 receptor antagonist, androgen receptor down regulator, and CYP17A1 inhibitor, the latter of which prevents the biosynthesis of androgens. As a CYP17A1 inhibitor, galeterone shows selectivity for 17,20-lyase over 17α-hydroxylase. Prostate cancer drug abiraterone and its analog galeterone are Δ5,3β-hydroxy steroids. Structures of these two agents are identical to endogenous steroid substrates (cholesterole, dehydroepiandorosterone and pregnenolone) for the 3β-hydroxysteroid dehydrogenase (3βHSD) of endocrine system. It has been reported that both of these agents are metabolized to 3-oxo-Δ4-steroids by 3βHSD in short period on oral administration. First metabolite 3-oxo-Δ4-abiraterone has more potent anti-prostate cancer prope ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 metastatic, hormone-refractory prostate cancer but failed to extend overall survival rates, and development was voluntarily terminated as a result. Orteronel is an androgen biosynthesis inhibitor. It selectively inhibits the enzyme CYP17A1 which is expressed in testicular, adrenal, and prostatic tumor tissues. CYP17 catalyzes two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by its 17α-hydroxylase activity, and (b) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by its 17,20-lyase activity. DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17 activity thus decreases circulating levels of testost ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
