Structural insights into the development of inhibitors for inositol phosphate kinases

The inositol phosphate signaling pathway has emerged as a compelling therapeutic target in a broad range of diseases, including osteoporosis, viral infections, metabolic disorders, and cancer metastasis. Inositol phosphates regulate essential cellular processes such as insulin signaling, nucleotide synthesis, DNA damage response, and phosphate homeostasis. Given this wide spectrum of physiological roles, the kinases responsible for inositol phosphate biosynthesis-namely IP3Ks, IPMK, ITPK1, IP5-2 K, IP6Ks, and PPIP5Ks-have attracted increased interest over the past decade. Accumulating evidence supports their potential as drug targets in the treatment of obesity, cancer, and aging-related conditions. In this review, structure-guided strategies, particularly those informed by high-resolution crystal structures, are examined for their role in accelerating the discovery and development of small-molecule inhibitors targeting inositol phosphate kinases. Structural insights, advances in therapeutic development, and future directions for improving inhibitor specificity and efficacy are discussed.