{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":50,"searchCount":0},"additional":{"omics_type":["Unknown"],"volume":["287(36)"],"submitter":["Song CH"],"pubmed_abstract":["Hormonal therapies, mainly combinations of anti-androgens and androgen deprivation, have been the mainstay treatment for advanced prostate cancer because the androgen-androgen receptor (AR) system plays a pivotal role in the development and progression of prostate cancers. However, the emergence of androgen resistance, largely due to inefficient anti-hormone action, limits the therapeutic usefulness of these therapies. Here, we report that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide (DIMN) acts as a novel anti-androgenic compound that may be effective in the treatment of both androgen-dependent and androgen-independent prostate cancers. Through AR structure-based virtual screening using the FlexX docking model, fifty-four compounds were selected and further screened for AR antagonism via cell-based tests. One compound, DIMN, showed an antagonistic effect specific to AR with comparable potency to that of the classical AR antagonists, hydroxyflutamide and bicalutamide. Consistent with their anti-androgenic activity, DIMN inhibited the growth of androgen-dependent LNCaP prostate cancer cells. Interestingly, the compound also suppressed the growth of androgen-independent C4-2 and CWR22rv prostate cancer cells, which express a functional AR, but did not suppress the growth of the AR-negative prostate cancer cells PPC-1, DU145, and R3327-AT3.1. Taken together, the results suggest that the synthetic compound DIMN is a novel anti-androgen and strong candidate for useful therapeutic agent against early stage to advanced prostate cancer."],"journal":["The Journal of biological chemistry"],"pagination":["30769-80"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3436320"],"repository":["biostudies-literature"],"pubmed_title":["Structure-based virtual screening and identification of a novel androgen receptor antagonist."],"pmcid":["PMC3436320"],"pubmed_authors":["Khadka DB","Gong EY","Cho WJ","Lee K","Yang SH","Cho SH","Song CH","Park E"],"view_count":["50"],"additional_accession":[]},"is_claimable":false,"name":"Structure-based virtual screening and identification of a novel androgen receptor antagonist.","description":"Hormonal therapies, mainly combinations of anti-androgens and androgen deprivation, have been the mainstay treatment for advanced prostate cancer because the androgen-androgen receptor (AR) system plays a pivotal role in the development and progression of prostate cancers. However, the emergence of androgen resistance, largely due to inefficient anti-hormone action, limits the therapeutic usefulness of these therapies. Here, we report that 6-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide (DIMN) acts as a novel anti-androgenic compound that may be effective in the treatment of both androgen-dependent and androgen-independent prostate cancers. Through AR structure-based virtual screening using the FlexX docking model, fifty-four compounds were selected and further screened for AR antagonism via cell-based tests. One compound, DIMN, showed an antagonistic effect specific to AR with comparable potency to that of the classical AR antagonists, hydroxyflutamide and bicalutamide. Consistent with their anti-androgenic activity, DIMN inhibited the growth of androgen-dependent LNCaP prostate cancer cells. Interestingly, the compound also suppressed the growth of androgen-independent C4-2 and CWR22rv prostate cancer cells, which express a functional AR, but did not suppress the growth of the AR-negative prostate cancer cells PPC-1, DU145, and R3327-AT3.1. Taken together, the results suggest that the synthetic compound DIMN is a novel anti-androgen and strong candidate for useful therapeutic agent against early stage to advanced prostate cancer.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Aug","modification":"2024-11-05T23:57:34.787Z","creation":"2019-03-27T00:57:41Z"},"accession":"S-EPMC3436320","cross_references":{"pubmed":["22798067"],"doi":["10.1074/jbc.M112.379107","10.1074/jbc.m112.379107"]}}