RGD Reference Report - A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats. - Rat Genome Database

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A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats.

Authors: Allan, G  Lai, MT  Sbriscia, T  Linton, O  Haynes-Johnson, D  Bhattacharjee, S  Dodds, R  Fiordeliso, J  Lanter, J  Sui, Z  Lundeen, S 
Citation: Allan G, etal., J Steroid Biochem Mol Biol. 2007 Jan;103(1):76-83. Epub 2006 Oct 17.
RGD ID: 10043311
Pubmed: PMID:17049844   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jsbmb.2006.07.006   (Journal Full-text)

The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (P<0.05 relative to orchidectomy alone). Using magnetic resonance imaging, the compound was found to partially prevent orchidectomy-induced loss of lean body mass. Our data show that selective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer treatmentISOAr (Rattus norvegicus)10043311; 10043311 RGD 
prostate cancer treatmentIDA 10043311; 10043311 RGD 
prostate cancer treatmentISOAR (Homo sapiens)10043311; 10043311 RGD 
Sarcopenia treatmentISOAr (Rattus norvegicus)10043311; 10043311 RGD 
Sarcopenia treatmentIDA 10043311 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ar  (androgen receptor)

Genes (Mus musculus)
Ar  (androgen receptor)

Genes (Homo sapiens)
AR  (androgen receptor)


Additional Information