CONCLUSIONS: Initial results of a BC genomic case-control study in an arsenic-exposed population are presented and raise candidate risk SNPs that need to be further validated in independent analyses. Additional insights into the genetics and biology of arsenic- related BC are also provided. However, further analysis is warranted after completion of recruitment. Source of Funding: Fondecyt Regular 1120987 MP68-17 NOVEL INTRAVESICAL THERAPIES IDENTIFIED FROM HIGH THROUGHPUT SCREENING Keidren Lewi*, Achuth Nair, Reema Railkar, Sam Brancato, Iawen Hsu, Quentin Li, Bethesda, MD; Xiaohu Zhang, Rajarshi Guha, Rockville, MD; Andrea Apolo, Bethesda, MD; Dan Theodorescu, Denver, CO; Craig Thomas, Marc Ferrer, Rockville, MD; Piyush Agarwal, Bethesda, MD INTRODUCTION AND OBJECTIVES: Since the approval of BCG, no new therapies have been introduced for bladder cancer. We utilized high throughput screening (HTS) to screen bladder cancer cell lines against oncology drugs. From these, we identified eight novel drugs as potential intravesical agents. METHODS: We screened 8 bladder cancer cell lines against 1,912 oncology drugs using a 48 hr cell proliferation assay with an ATPÀbased readout (CellTiterGlo) to determine activity and potency of compounds in a dose response manner. From the most active com- pounds, we identified favorable compounds for intravesical therapy: molecular size of 700-1000 g/mol and lipophilicity measured by Topo- graphical Polar Surface Area < 90 (TPSA). These compounds were analyzed for cytotoxicity in an MTS cell proliferation assay to determine the IC50s of these drugs in 6 cell lines (3 not used in the original screen). RESULTS: The initial screen identified 95 compounds active in 8 cell lines. The top 50 compounds were further analyzed for molecular size of 700-1000 g/mol and TPSA<90. This identified mitomycin C and 8 novel compounds (Table 1) that were further tested by MTS in 6 bladder cancer cell lines. The top 3 agents were: YM-155, flavopiridol, and bardoxolone methyl with IC 50s that ranged from 1-30 nm, 0.2-12 nm, and 0.8-2 nm respectively in the 6 cell lines. The MTS curves are included in Figures 1-3. CONCLUSIONS: HTS is an efficient way to elicit novel targets and therapies for cancer. We identified novel candidates for intravesical therapy and are currently elucidating the mechanism of action of these drugs. Table 1 Potential Intravesical Agents Identified from HTS Compound Molecular Weight (g/mol) Topographical Polar Surface Area Target YM-155 443.2 78 Survivin inhibitor, BIRC5 Expression Inhibitor ARN-509 477.4 121 Androgen Receptor Antagonists AZD-8055 465.5 93.1 mTORC1/2 Inhibitor Flavopiridol 401.8 90.2 CDK1/2/4/6/7/9 Inhibitor Ponatinib 532.6 65.8 FGFR Inhibitor Cabozantinib 501.5 98.8 VEGFR-2 Inhibitor, Flt3/HGFR/KIT/ RET/ inhibitor, Tie2 Receptor Inhibitor Bardoxolone Methyl 505.7 84.2 NF-kappaB signaling Inhibitor, Production Inhibitor AT-7519 382.2 98.9 CDK inhibitor Mitomycin C 334.3 127.9 Alkylating Agent e864 THE JOURNAL OF UROLOGY â Vol. 193, No. 4S, Supplement, Monday, May 18, 2015