The industry of nonsteroidal androgens has grown tremendously
Posted by kinsxu on Wednesday, November 9, 2011
The industry of nonsteroidal androgens,and particularly selective
androgen receptor modulators (SARMs), has grown tremendously because
the first report in 1998. Many of the major pharmaceutical companies
have recently published in vivo characterizations of tissue selective
AR agonists, as well as rate of latest contributionsto our field
carries on accelerate. The increase of the field has triggered a
broadening from the chemical space originally occupied via the
traditional steroidal agonists (not shown) and nonsteroidal
antagonists, whose use is restricted by prostate liability and
insufficient tissue-selectivity, respectively. Many chemically
distinct putative AR agonist templates are actually reported, with
fewer having demonstrated in vivo tissue-selectivity for anabolic
tissues (i.e., SARMs), as summarized in Supplementary File 1. This
pharmacophoric diversity portends pharmacokinetic (PK) and
pharmacodynamic (PD) diversity across many chemotypes, suggesting the
opportunity of broad therapeutic application for SARMs. The concept of
SARM is going to be reviewed with emphasis provided to groups with all
the most satisfactory preclinical PK/PD characterizations, or clinical
data. Other excellent SARM surveys are available.
Several groups have advanced SARMs for the clinic for specific indications.The existing clinical practices, followed with the rationale and results (where available) of such trials, are briefly discussed below.Age-related decline in muscle mass ends up with the clinical condition often called sarcopenia in older individuals. A rise in the elderly population has led to the growing number of frail people which might be struggling to performactivities of day to day living so are thus looking for
assisted-care.While enhancing protein intake and exercise programs offer way to combat the muscles loss occurring with aging, hormonal remedies are prone to show more drastic effects. An agent capable of selectively increasing muscle performance without androgenic side effects for example prostate increase in men and virilization in women (negative effects of steroidal androgens) is desirable for that management of sarcopenia. A Phase IIa study with the drug Ostarine
has shown significant improvement in the ability of healthy, elderly individuals to climb stairs, combined with significant increases in lean body mass and decreases in fat mass only for 86 days. Insufficient PSA increase in males and hair regrowth ladies further corroborated selective anabolic results of Ostarine TM. Reductions in serum lipids were observed. However, LDL/HDL ratios stay in the reduced cardiovascular risk category. The occurrence of adverse events were otherwise similar in the placebo and treatment groups.Thus, clinical proof of the advantages of SARM answer to improving strength exists and shows promise for the treatment of age-related decline in muscle strength, and also other related indications being pursued by Pharmacopeia (age-related functional decline) and Ligand Pharmaceuticals (frailty), both having completed Phase I trials.
Several groups have advanced SARMs for the clinic for specific indications.The existing clinical practices, followed with the rationale and results (where available) of such trials, are briefly discussed below.Age-related decline in muscle mass ends up with the clinical condition often called sarcopenia in older individuals. A rise in the elderly population has led to the growing number of frail people which might be struggling to performactivities of day to day living so are thus looking for
assisted-care.While enhancing protein intake and exercise programs offer way to combat the muscles loss occurring with aging, hormonal remedies are prone to show more drastic effects. An agent capable of selectively increasing muscle performance without androgenic side effects for example prostate increase in men and virilization in women (negative effects of steroidal androgens) is desirable for that management of sarcopenia. A Phase IIa study with the drug Ostarine
has shown significant improvement in the ability of healthy, elderly individuals to climb stairs, combined with significant increases in lean body mass and decreases in fat mass only for 86 days. Insufficient PSA increase in males and hair regrowth ladies further corroborated selective anabolic results of Ostarine TM. Reductions in serum lipids were observed. However, LDL/HDL ratios stay in the reduced cardiovascular risk category. The occurrence of adverse events were otherwise similar in the placebo and treatment groups.Thus, clinical proof of the advantages of SARM answer to improving strength exists and shows promise for the treatment of age-related decline in muscle strength, and also other related indications being pursued by Pharmacopeia (age-related functional decline) and Ligand Pharmaceuticals (frailty), both having completed Phase I trials.