Abstract 4271: Discovery of NNC 05-2090, a small molecule antagonist of the neuromedin U receptor 2 for glioma treatment

Abstract Gliomas account for approximately 30% of all brain and central nervous system tumors, and 80% of all malignant brain tumors. Despite their high frequency, the causes of gliomas remain largely unknown. Temozolomide is the standard treatment for glioma, but its efficacy is limited due to the high rate of recurrence and the development of drug resistance in glioma patients. Therefore, discovering novel therapeutic targets and drugs is crucial to improving survival rate for glioma patients. This study aims to investigate the functions of neuromedin U receptor 2 (NMUR2) as a novel target for glioma and to identify NMUR2-specific regulatory drugs. NMUR2 is highly expressed in glioma tissue, and its overexpression promotes cell proliferation and migration, while its knockdown suppresses these effects. RNA sequencing analysis revealed that NMUR2 knockdown downregulates cell cycle-related genes. STAT5, a transcription factor, mediates the link between NMUR2 and cell cycle regulation. To discover an NMUR2-specific antagonist, we performed cell-based drug screening with 6, 331 repurposing drugs and finally identified NNC 05-2090. The NNC 05-2090 treatment in glioma cells reduced cell cycle progression through its downstream signaling pathway. Additionally, we observed a synergistic effect between NNC 05-2090 and temozolomide in both in vitro and in vivo. In conclusion, this study suggests that NMUR2 is a promising novel target, and its antagonist, NNC 05-2090, combined with temozolomide, might offer a promising strategy to improve glioma treatment. Citation Format: Yuna Roh, Taesang Son, Jang-Seong Kim, Tae-Su Han, Hyun Seung Ban, Seon-Kyu Kim. Discovery of NNC 05-2090, a small molecule antagonist of the neuromedin U receptor 2 for glioma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4271.