title: A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats.
abstract: Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-28330835 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle, stimulating maximal growth at a dose of 10 mg/kg. At the same time, JNJ-28330835 reduced prostate weight in intact rats by a mean of 30% at 10 mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging (MRI) to monitor body composition, it prevented half of the loss of lean body mass associated with orchidectomy, and restored about 30% of lost lean mass to aged orchidectomized rats. It had agonist effects on markers of both osteoclast and osteoblast activity, suggesting that it reduces bone turnover. In a model of sexual behavior, JNJ-28330835 enhanced the preference of ovariectomized female rats for sexually intact male rats over nonsexual orchidectomized males. JNJ-28330835 is a prostate-sparing SARM with the potential for clinically beneficial effects in muscle-wasting diseases and sexual function disorders.
authors.affiliation: Reproductive Therapeutics, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ, 08869, USA. gallan4@prdus.jnj.com
authors.forename: George F
authors.initials: GF
authors.lastname: Allan
authors.forename: Pamela
authors.initials: P
authors.lastname: Tannenbaum
authors.forename: Tifanie
authors.initials: T
authors.lastname: Sbriscia
authors.forename: Olivia
authors.initials: O
authors.lastname: Linton
authors.forename: Muh-Tsann
authors.initials: MT
authors.lastname: Lai
authors.forename: Donna
authors.initials: D
authors.lastname: Haynes-Johnson
authors.forename: Sheela
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Xuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
authors.forename: Scott G
authors.initials: SG
authors.lastname: Lundeen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000097:blood; D006984:Hypertrophy / Q000139:chemically induced; D008297:Male; D009132:Muscles / Q000033:anatomy & histology / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects*
chemical_list: D006728:Hormones; C527554:JNJ-28330835; D011720:Pyrazoles