title: Effects of SP500263, a novel selective estrogen receptor modulator, on bone, uterus, and serum cholesterol in the ovariectomized rat.
abstract: We describe here the activity of a novel selective estrogen receptor modulator, SP500263. When given to adult ovariectomized (OVX) rats for 28 days at doses of 0.3, 1, or 3 mg/kg/day, we found that SP500263 partially protected against OVX-induced loss of bone mineral content in the distal ends of femurs and in the whole bone. SP500263 also antagonized the OVX-induced increase in body weight. However, unlike 17beta-estradiol, SP500263 at efficacious doses did not prevent the OVX-induced loss in uterine wet weight. A small but significant effect on uterine wet weight was noted with raloxifene dosed at 1 mg/kg. As expected, SP500263 but not raloxifene acted as an estrogen antagonist on the uterus in adult rats when administered for 7 days at 30 mg/kg/day. Finally, SP500263 had no statistically significant effects on total serum cholesterol and serum triglycerides in OVX rats treated for 28 days. Raloxifene had no significant effects on body weight, bone mineral content, and serum cholesterol or triglycerides in the OVX-rat model. In summary, SP500263 is a new orally active SERM that acts in rats as an estrogen agonist on bone without causing uterine stimulatory effects.
authors.affiliation: Celgene Corp., 4550 Towne Centre Court, San Diego, CA 92121, USA.
authors.forename: M Kung
authors.initials: MK
authors.lastname: Sutherland
authors.forename: H
authors.initials: H
authors.lastname: Brady
authors.forename: L M
authors.initials: LM
authors.lastname: Gayo-Fung
authors.forename: J
authors.initials: J
authors.lastname: Leisten
authors.forename: S G
authors.initials: SG
authors.lastname: Lipps
authors.forename: J A
authors.initials: JA
authors.lastname: McKie
authors.forename: E
authors.initials: E
authors.lastname: O'Leary
authors.forename: N
authors.initials: N
authors.lastname: Patnaik
authors.forename: D W
authors.initials: DW
authors.lastname: Anderson
authors.forename: S S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: B
authors.initials: B
authors.lastname: Stein
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood*; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011859:Radiography; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000187:drug effects* / Q000473:pathology
chemical_list: D003374:Coumarins; D010880:Piperidines; C448221:SP500263; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D020849:Raloxifene Hydrochloride; D002784:Cholesterol