ArticleNature communications2021
The enzymatic activity of inositol hexakisphosphate kinase controls circulating phosphate in mammals.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Analytical methods and tools for studying inositol phosphates.FEBS letters · 2026Review
- Targeting the Ip6k2-Runx2 axis disrupts osteoblast-osteoclast coupling to treat osteoporosis.Nature communications · 2026Article
- Oncometabolite 5-IPNature chemical biology · 2026Article
- Role of Inositol Hexakisphosphate Kinases in Vascular Smooth Muscle Cell Calcification.International journal of molecular sciences · 2026Article
- Phosphorus-specific, liquid chromatography inductively coupled plasma mass spectrometry for analysis of inositol phosphate and inositol pyrophosphate metabolism.The Biochemical journal · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1.Molecular cell · 2025Article
- Global profiling of N-terminal cysteine-dependent degradation mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling withJournal of the American Chemical Society · 2025Article
- Transport and InsPNature communications · 2025Article
- Structural insights into the mechanism of phosphate recognition and transport by XPR1.Nature communications · 2025Article
- Enabling Technologies for the Dissection of Inositol Pyrophosphate Physiology.Methods in molecular biology (Clifton, N.J.) · 2025Article
- IP6 Kinase Inhibitor Screening Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Enzymatic Synthesis of Inositol Pyrophosphates.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Extensive protein pyrophosphorylation revealed in human cell lines.Nature chemical biology · 2024Article
- Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia-reperfusion injury by elevating plasma adiponectin.Cardiovascular research · 2024Article
- Insights into the roles of inositol hexakisphosphate kinase 1 (IP6K1) in mammalian cellular processes.The Journal of biological chemistry · 2024Review
- Shaping the Future of Obesity Treatment: In Silico Multi-Modeling of IP6K1 Inhibitors for Obesity and Metabolic Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circulating phosphate levels are tightly controlled within a narrow range in mammals. By using a novel small-molecule inhibitor, we show that the enzymatic activity of inositol hexakisphosphate kinases (IP6K) is essential for phosphate regulation in vivo. IP6K inhibition suppressed XPR1, a phosphate exporter, thereby decreasing cellular phosphate export, which resulted in increased intracellular ATP levels. The in vivo inhibition of IP6K decreased plasma phosphate levels without inhibiting gut intake or kidney reuptake of phosphate, demonstrating a pivotal role of IP6K-regulated cellular phosphate export on circulating phosphate levels. IP6K inhibition-induced decrease in intracellular inositol pyrophosphate, an enzymatic product of IP6K, was correlated with phosphate changes. Chronic IP6K inhibition alleviated hyperphosphataemia, increased kidney ATP, and improved kidney functions in chronic kidney disease rats. Our results demonstrate that the enzymatic activity of IP6K regulates circulating phosphate and intracellular ATP and suggest that IP6K inhibition is a potential novel treatment strategy against hyperphosphataemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.