BMS-564,929 is an investigational

selective androgen receptor modulator Selective Androgen Receptor Modulators or SARMs are a class of androgen receptor ligands that maintain some of the desirable effects of androgens, such as preventing osteoporosis and muscle loss while reducing risks of developing prostate cancer ...

(SARM) which is being developed by

Bristol-Myers Squibb The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...

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

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

mass and

strength Strength may refer to: Physical strength *Physical strength, as in people or animals *Hysterical strength, extreme strength occurring when people are in life-and-death situations *Superhuman strength, great physical strength far above human ca ...

, reduction in

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...

and

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 ...

. Treatment with exogenous

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 system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

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 both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...

, which can lead to

benign prostatic hypertrophy 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 ...

and even

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 sur ...

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

anabolic Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-do ...

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 referen ...

for muscle tissue over prostate) and in studies on castrated rats it was shown to counteract 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 (GnRH) ...

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 more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone (medication), testosterone as well as synthetic androgens that are structurally related ...

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; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...

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. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...

{{Androgen receptor modulators Secondary alcohols Bristol Myers Squibb Chlorobenzenes Imides Lactams Nitriles Pyrroloimidazoles Selective androgen receptor modulators Ureas