Abstract
A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Administration, Cutaneous
-
Anabolic Agents / administration & dosage
-
Anabolic Agents / chemical synthesis
-
Anabolic Agents / therapeutic use*
-
Androgen Antagonists / administration & dosage
-
Androgen Antagonists / chemical synthesis
-
Androgen Antagonists / therapeutic use*
-
Aniline Compounds / administration & dosage
-
Aniline Compounds / chemical synthesis
-
Aniline Compounds / therapeutic use*
-
Animals
-
Cholesterol, HDL / metabolism
-
Humans
-
Hypercholesterolemia / chemically induced
-
In Vitro Techniques
-
Liver / drug effects
-
Liver / metabolism
-
Macaca fascicularis
-
Male
-
Models, Molecular
-
Muscular Atrophy / drug therapy*
-
Nitriles / administration & dosage
-
Nitriles / chemical synthesis
-
Nitriles / therapeutic use*
-
Orchiectomy
-
Prostatic Hyperplasia / chemically induced
-
Rats
-
Skin Absorption
-
Structure-Activity Relationship
Substances
-
2-chloro-4-((2-hydroxy-2-methylcyclopentyl)amino)-3-methylbenzonitrile
-
Anabolic Agents
-
Androgen Antagonists
-
Aniline Compounds
-
Cholesterol, HDL
-
Nitriles