Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Prostate cancer is the most common male cancer and the second leading cause of cancer-related deaths in developed countries. The androgen receptor (AR) is a key molecular target in the etiology and progression of the disease where the early stages of prostate cancer tumor growth are androgen dependent and respond well to androgen ablation and androgen receptor antagonists. However, castration-resistant prostate cancer (CRPC) typically develops in 1-2 years after androgen deprivation therapy and AR antagonist administration. Despite promising results from the recently approved second-generation AR antagonist Enzalutamide (MDV3100), CRPC remains a largely unmet medical need with less than a 15% 5-year survival rate.</jats:p>
<jats:p>This poster introduces the discovery of a novel series of significantly structurally distinct small-molecule androgen antagonists from current therapeutics with promising biological profiles in (1) an FP binding assay, (2) a GeneBlazerTM functional assay and (3) a study of anti-proliferative activity against LNCaP cell growth. One of several promising compounds from a current collection of ∼100 analogs is exemplified by AR002.</jats:p>
<jats:p>CompoundFP AR binding assay (IC50)GeneBlazerTM β-lactamase reporter assay (IC50)LNCAP cell growth inhibition (GI50)AR002328.7 nM557 nM2.3 μMEnzalutamide920 nM1150 nM11.65 μMBicalutamide145 nM1370 nM30.68 μM</jats:p>
<jats:p>In summary, a novel class of AR antagonists has been identified, encouragingly demonstrating potent activity against AR and inhibition of cell growth in the prostate specific line LNCaP.</jats:p>
<jats:p>Citation Format: Arthur Y. Shaw, Vijay Gokhale, Christopher Hulme, Steven P. Stratton. Promising early-stage novel androgen receptor antagonists in head-head comparisons with Enzalutamide and Bicalutamide. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2524. doi:10.1158/1538-7445.AM2014-2524</jats:p>