Fluasterone, also known as 3β-dehydroxy-16α-fluoro- or 16α-fluoroandrost-5-en-17-one, is a fluorinated

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

analogue of dehydroepiandrosterone (DHEA) which was under investigation by Aeson Therapeutics for a variety of therapeutic indications including cancer,

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, h ...

s, diabetes, obesity, and traumatic brain injury among others but was ultimately never marketed. It is a modification of DHEA in which the C3β hydroxyl has been removed and a hydrogen atom has been

substituted A substitution reaction (also known as single displacement reaction or single substitution reaction) is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group. Substitution reactions ar ...

with a

fluorine Fluorine is a chemical element with the symbol F and atomic number 9. It is the lightest halogen and exists at standard conditions as a highly toxic, pale yellow diatomic gas. As the most electronegative reactive element, it is extremely reacti ...

atom at the C16α position. Fluasterone reached

phase II Phase II, Phase 2 or Phase Two may refer to: Media * Marvel Cinematic Universe: Phase Two, six American superhero films from 2013–2015 * ''Star Trek: Phase II'', an unrealized television series based on the characters of Gene Roddenberry's ''S ...

clinical trials prior to the discontinuation of its development. The mechanism of action of DHEA and fluasterone is unknown. However, similarly to DHEA but more strongly, fluasterone is a potent uncompetitive inhibitor of (K_i = 0.5 μM versus 17 μM for DHEA). The drug retains the antiinflammatory, antihyperplastic, chemopreventative,

antihyperlipidemic Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins such as cholestero ...

antidiabetic Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thus ...

, and antiobesic, as well as certain immunomodulating activities of DHEA, much but not all of which it is thought may possibly be mediated via G6PDH inhibition (with some experimental evidence to support this notion available). Conversely, unlike DHEA, fluasterone has minimal or no androgenic or estrogenic activity, and due to the presence of the fluorine atom at the C16α position, its metabolism at the C17α position is

sterically hindered Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

and thus it cannot be metabolized into androgens like testosterone or estrogens like estradiol. Also in contrast to DHEA, fluasterone does not produce

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

or seizures in animals and hence is not thought to interact with the GABA_A receptor. In addition, unlike DHEA, fluasterone has reduced or no effects as a peroxisome proliferator (i.e., lacks activity at the ), and hence does not pose a risk of liver toxicities such as hepatomegaly or

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

. It is for these reasons that fluasterone was developed and was considered to be advantageous to DHEA. Due to extensive first-pass hepatic and/or gastrointestinal metabolism, very high doses of DHEA and fluasterone are necessary for effectiveness. In animals, the

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

of fluasterone is increased 40-fold when administered parenterally, and for this reason, a non- oral formulation of fluasterone was selected for clinical development. However, the development of fluasterone was nonetheless stopped reportedly due to its low potency and low oral bioavailability, which are said to have rendered it unsuitable for clinical use.

References

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External links

Fluasterone - AdisInsight
Abandoned drugs Androstanes Anti-diabetic drugs Anti-inflammatory agents Antineoplastic drugs Antiobesity drugs Chemopreventive agents Organofluorides Hypolipidemic agents Immunomodulating drugs Ketones