Design, Synthesis, and Cellular Characterization of a New Class of IPMK Kinase Inhibitors.

ABSTRACT: The kinase activity of human inositol phosphate multikinase (IPMK) is required for the synthesis of higher-order inositol phosphate signaling molecules, regulation of gene expression, and control of the cell cycle. Here, we report a novel series of highly potent IPMK inhibitors. The first-generation IPMK inhibitor 1 (UNC7437) decreased cellular proliferation and tritiated inositol phosphate levels in metabolically labeled human U251-MG glioblastoma cells. It also impacted the transcriptome of these cells, selectively regulating 993 genes enriched in cancer, epithelial-to-mesenchymal transition (EMT), and inflammatory and viral infection pathways, consistent with anticancer growth activity. Extensive optimization of 1 led to 14 (UNC9750) with improved pharmacokinetic pr

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12362615 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature