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• W1896892103 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20065345 Complete androgen ablation (LHRH agonists and antiandrogens) is the gold standard treatment for metastatic prostate cancer. BMS-641988 is a recently identified novel antiandrogen with superior potency and efficacy compared to bicalutamide (Casodex®, AstraZenceca). Global mechanistic similarities and differences between the two antiandrogens and castration were assessed by gene and protein expression in two different in vivo systems. In the first noted, the gene expression profiles of CWR22 human prostate tumors implanted into mice treated with a) vehicle, b) BMS-641988, c) bicalutamide, and d) castration, were analyzed by Affymetrix and QT-RT-PCR after 1, 2, and 7 days of treatment. These studies show that BMS-641988 treatment promotes an expression profile more similar to castration than bicalutamide, especially at days 2 and 7. Several genes previously reported to be regulated by the androgen receptor such as IGBP3, AR, FKBP5, and NKX3-1, were also identified in this experiment. The second in vivo model consisted of mature male rats treated for 14 days with each antiandrogen or castration. At the end of the study serum and ventral prostates were collected and subject to proteomic analysis. At the same dose, the serum profiles of castrated rats were more similar to BMS641988 than to bicalutamide. In addition, there were a substantially larger number of peptides showing a positive dose dependence with BMS-641988 than with bicalutamide. Together with the pharmacological profile these differences in global gene and protein expression suggest differences between BMS-641988 from bicalutamide and support BMS-641988 as a new clinical candidate." @default.
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• W1896892103 date "2006-04-15" @default.
• W1896892103 modified "2023-09-26" @default.
• W1896892103 title "Preclinical assessment of gene expression and proteomic profiles promoted by the novel antiandrogen BMS-641988, bicalutamide and castration." @default.
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