Abstract 1664: 4-Bromophenylhydrazinyl benzenesulfonylphenylureas inhibit indoleamine 2,3-dioxygenase in vitro and in vivo

Indoleamine 2,3-dioxygenase has been considered as a promising anti-cancer drug target. Several pharmaceutical companies, including Pfizer, Merck, and Bristol-Myers Squibb, are known to be in pursuit of IDO inhibitors, and Incyte recently reported good results in the phase II clinical trial of the IDO inhibitor Epacadostat. In previous work, we developed a series of IDO inhibitors based on a high-throughput screening core structure, sulfonylhydrazide. Further, we developed the 4-bromophenylhydrazinyl benzenesulfonylphenylurea, as a potent IDO inhibitor with an IC50 value within 100 nM in inhibiting IDO in vitro. This compound demonstrated a 30% reduction in tumor weight in a murine CT26 syngeneic model on day 18 with 100 mg/kg oral administration twice daily, indicating that the 4-bromophenylhydrazinyl benzenesulfonylphenylurea may have potential for further investigation in the development of anti-tumor drugs. Citation Format: Shau-Hua Ueng, Ching-Chuan Kuo, Shu-Yu Lin, Teng-Kuang Yeh, Jen-Shin Song, Ming-Shiu Hung, Chiung-Tong Chen. 4-Bromophenylhydrazinyl benzenesulfonylphenylureas inhibit indoleamine 2,3-dioxygenase in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1664.