Abstract LB-099: A high-throughput screen of approved drugs uncovers a synergistic interaction targeting prostate cancer

Abstract

Abstract Libraries of approved drugs contain some of the best studied small molecules and represent invaluable resources for drug repurposing and chemical biology studies. Access to comprehensive libraries of clinical compounds is limited and these collections are otherwise difficult to arrange. Using cheminformatics approaches we have assembled a non-redundant set of representative FDA-approved small molecules that we call the CeMM Library of Unique Drugs (CLOUD). The CLOUD covers the chemical and biological space of approved drugs, contains active forms of prodrugs, and can be screened at clinically relevant concentrations. In a combinatorial viability screen of the CLOUD we uncovered a synergistic interaction between two approved drugs. We show that the concomitant administration of these two small molecules induces apoptosis in the androgen receptor (AR)-dependent prostate cancer cell line LNCaP. Mechanistically, the combination affects AR signaling and the stability of the receptor itself. We are currently dissecting further aspects of the mechanism of action and performing in vivo experiments. Altogether, our data suggest that the combination of these two drugs can be repurposed for the treatment of prostate cancer. Citation Format: Marco P. Licciardello, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Gerhard Dürnberger, Vladimir Ivanov, Jacques Colinge, Stefan Kubicek. A high-throughput screen of approved drugs uncovers a synergistic interaction targeting prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-099. doi:10.1158/1538-7445.AM2015-LB-099