title: 2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy.
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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Saeed
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Vaught
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Kostas
authors.initials: K
authors.lastname: Gavardinas
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Donald
authors.initials: D
authors.lastname: Matthews
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Green
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Pablo Garcia
authors.initials: PG
authors.lastname: Losada
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bullock
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Calvert
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Nita J
authors.initials: NJ
authors.lastname: Patel
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Sweetana
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Judith W
authors.initials: JW
authors.lastname: Henck
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: John G
authors.initials: JG
authors.lastname: Luz
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Jadhav
mesh_terms: D000279:Administration, Cutaneous; D045930:Anabolic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D000814:Aniline Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D000818:Animals; D008076:Cholesterol, HDL / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008958:Models, Molecular; D009133:Muscular Atrophy / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D009919:Orchiectomy; D011470:Prostatic Hyperplasia / Q000139:chemically induced; D051381:Rats; D012869:Skin Absorption; D013329:Structure-Activity Relationship
chemical_list: C000608233:2-chloro-4-((2-hydroxy-2-methylcyclopentyl)amino)-3-methylbenzonitrile; D045930:Anabolic Agents; D000726:Androgen Antagonists; D000814:Aniline Compounds; D008076:Cholesterol, HDL; D009570:Nitriles