It looks like LGND has many presentations at the Endocrine Society Conference. Here's an anti-androgen abstract scheduled for presentation tomorrow:
P3-126 EFFECTS OF THE NOVEL NON-STEROIDAL ANTI-ANDROGEN, LG120907, IN SUPPRESSION OF THE R3327H DUNNING RAT PROSTATE TUMOR Xiao-Ning Wang1, Chau Nguyen1, Rene Prudente1, Murriel Wagoner1, William Hunter1, William T Schrader1, Marco M Gottardis1, 1Depts of Endocrine Research and Pharmacology, Ligand Pharmaceuticals Inc., San Diego, CA,
Non-steroidal anti-androgens, such as flutamide and bicalutamide, have been used as standard agents for the adjuvant treatment of advanced prostate cancer. Here we describe the characterization of a novel anti-androgen (AA) pharmacophore, LG120907, which is active in the R3327H Dunning prostate tumor model. In initial tests of prostate organ weight suppression in intact rats the IC50's of LG120907, flutamide and bicalutamide were 20, 20 and 5mg/kg, respectively. Chronic administration of LG120907 in tumor-bearing Copenhagen male rats (20mg/kg oral daily dosing for 14 weeks) significantly retarded the growth of tumors down to 17% of the tumor volume of vehicle-treated animals. LG120907, flutamide and bicalutamide were all equally efficacious in inhibiting tumor growth in this model. In these same animals, we also evaluated increases in serum gonadotropin and sex hormone concentrations. LG120907 and bicalutamide increased serum LH only 2-fold compared to vehicle-treated animals. By comparison, flutamide increased serum LH 4-fold. No increases in serum testosterone concentrations were noted in LG120907-treated animals compared to flutamide-treated (10-fold increase) and bicalutamide-treated (3-fold increase) animals. Finally, tumor-bearing male animals from the Dunning studies were mated to virgin female rats after 9-14 weeks of therapy. Pregnancy rates for females mated with vehicle-, LG120907-, bicalutamide- or flutamide-treated males were 75%, 80%, 30% and 0%, respectively. At term, 75% of females in vehicle- and LG120907-mated groups delivered pups, compared to only 23% of females mated to bicalutamide-treated males. The average litter size was greater in vehicle-treated and LG120907-treated animals (14.0 and 13.9 pups/litter, respectively) compared to the bicalutamide-male mated females (8.8 pups/litter). These studies indicate that LG120907 can be used as a template for developing anti-androgen pharmacophores which avoid adverse CNS and fertility side-effects for the chronic treatment of malignant or benign disease.
Presentation Date, Time, Room: 26-Jun-98, 11:00A, CC-Exhibit Hall
L=Special Session, N=Nurse Symposium, OR=Oral, P=Poster, S=Symposium |
