Abstract B010: Determining the cancer cell sensitivity to IPMK-ATP competitive inhibitors

Abstract Human inositol phosphate multikinase (IPMK) is an inositol kinase that plays a significant role in many cellular processes. IPMK activity is required for the production of all higher-order inositol phosphate species (IP5, IP6, IP7 and IP8) which are signaling molecules that regulate cell proliferation. It is known in several cancers that normal cellular functions become dysregulated resulting increased cellular growth. IPMK has been linked to glioblastoma and could be relevant in therapeutic applications, however it is unknown what other cancers IPMK may be connected to. This study aims to determine the activity of a novel IPMK inhibitor we recently published, in cancer cell lines to determine the effect on cellular proliferation. This IPMK inhibitor, UNC9750, was used to treat in U251-MG glioblastoma cells, our results show suppression of growth in this cell line. These results confirm previous observations, validating our assay and approach. We now seek to screen an additional 10 cancer cell lines with UNC9750 in similar cell proliferation assays, while in parallel we conduct high throughput screening on the NCI-60 panel, in collaboration with the National Cancer Institute. These data will be used to identify and characterize cancer cell lines most sensitive and most resistant to IPMK inhibitors, indicating cancers future studies will focus on. We also plan to analyze the transcriptomes regulated by UNC9750, comparing differentially expressed genes between cancer lines that are sensitive vs. resistant to UNC9750, and identify what unique gene signatures exist. We expect these approaches to reveal potential cancer cell lines sensitive and resistant to UNC9750, and what genes are differentially expressed in each of these cellular backgrounds. Together, the data will inform which cancers are pursued for future clinical applications of UNC9750, a potent IPMK inhibitor. Citation Format: Jasmyn K. Brown, Kimora L. Hudson, Raymond D. Blind. Determining the cancer cell sensitivity to IPMK-ATP competitive inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr B010.