BMS-564,929 is an investigational

selective androgen receptor modulator Selective androgen receptor modulators (SARMs) are a class of drugs that tissue selectivity, selectively activate the androgen receptor in specific tissue (biology), tissues, promoting muscle and bone growth while having less effect on male re ...

(SARM) which is being developed by

Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...

for treatment of the symptoms of age-related decline in androgen levels in men (" andropause"). These symptoms may include depression, loss of

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

mass and

strength Strength may refer to: Personal trait *Physical strength, as in people or animals *Character strengths like those listed in the Values in Action Inventory *The exercise of willpower Physics * Mechanical strength, the ability to withstand ...

, reduction in

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

and

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

. Treatment with exogenous

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

is effective in counteracting these symptoms but is associated with a range of side effects, the most serious of which is enlargement of the

prostate gland The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

, which can lead to

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, urinary retention, inability t ...

and even

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. This means there is a clinical need for selective androgen receptor modulators, which produce

anabolic Anabolism () is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catab ...

effects in some tissues such as muscle and bone, but without stimulating androgen receptors in the prostate. BMS-564,929 is one such compound currently in early human clinical trials, which is an orally active, potent, and selective agonist for androgen receptors ( Ki 2.1nM, 20x

functional selectivity Functional selectivity (or agonist trafficking, biased agonism, biased signaling, ligand bias, and differential engagement) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the end ...

for muscle tissue over prostate) and in studies on castrated rats it was shown to counteract the decrease in muscle mass over time, and at higher doses even increased muscle mass, without significantly affecting prostate tissue. It does however vastly reduce

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

levels, it being an astonishing 33× more suppressive compound than testosterone, which may be a problem in human clinical use. Selective androgen receptor modulators may also be used by athletes to assist in training and increase physical stamina and fitness, potentially producing effects similar to

anabolic steroid Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor (AR). Anabolism, Anaboli ...

s but with significantly fewer side effects. For this reason, SARMs have already been banned by the

World Anti-Doping Agency The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...

since January 2008 despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs are currently being developed.

References

External links

Crystal Structure Of The Rat Androgen Receptor Ligand Binding Domain Complex With Bms-564929
at

Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...

{{Androgen receptor modulators Secondary alcohols Drugs developed by Bristol Myers Squibb Chlorobenzene derivatives Imides Lactams Nitriles Pyrroloimidazoles Selective androgen receptor modulators Ureas