ArticleACS pharmacology & translational science2021
Identification of Small-Molecule Inhibitors of Human Inositol Hexakisphosphate Kinases by High-Throughput Screening.
Article in ACS pharmacology & translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Molecular deep learning at the edge of chemical space.Nature machine intelligence · 2026Article
- Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IPACS infectious diseases · 2025Article
- IP6 Kinase Inhibitor Screening Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Shaping the Future of Obesity Treatment: In Silico Multi-Modeling of IP6K1 Inhibitors for Obesity and Metabolic Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Fragment-Based Screening Identifies New Quinazolinone-Based Inositol Hexakisphosphate Kinase (IP6K) Inhibitors.ACS medicinal chemistry letters · 2023Article
- Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Article
- The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System.Biomolecules · 2023Review
- β-lapachone regulates mammalian inositol pyrophosphate levels in an NQO1- and oxygen-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling.Biomolecules · 2023Article
- A Shift in Thinking: Cellular Thermal Shift Assay-Enabled Drug Discovery.ACS medicinal chemistry letters · 2023Review
- TNP Analogues Inhibit the Virulence Promoting IPBiomolecules · 2022Article
- Diabetes and its Complications.ACS pharmacology & translational science · 2022Article
- Development of Novel IP6K Inhibitors for the Treatment of Obesity and Obesity-Induced Metabolic Dysfunctions.Journal of medicinal chemistry · 2022Article
- Whole BodyInternational journal of molecular sciences · 2022Article
- Pleiotropic actions of IP6K1 mediate hepatic metabolic dysfunction to promote nonalcoholic fatty liver disease and steatohepatitis.Molecular metabolism · 2021Article
- Dissecting the activation of insulin degrading enzyme by inositol pyrophosphates and their bisphosphonate analogs.Chemical science · 2021Article
- The enzymatic activity of inositol hexakisphosphate kinase controls circulating phosphate in mammals.Nature communications · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inositol hexakisphosphate kinases (IP6Ks) catalyze pyrophosphorylation of inositol hexakisphosphate (IP6) into inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (IP7), which is involved in numerous areas of cell physiology including glucose homeostasis, blood coagulation, and neurological development. Inhibition of IP6Ks may be effective for the treatment of Type II diabetes, obesity, metabolic complications, thrombosis, and psychiatric disorders. We performed a high-throughput screen (HTS) of 158 410 compounds for IP6K1 inhibitors using a previously developed ADP-Glo Max assay. Of these, 1206 compounds were found to inhibit IP6K1 kinase activity by more than 25%, representing a 0.8% hit rate. Structural clustering analysis of HTS-active compounds, which were confirmed in the dose-response testing using the same kinase assay, revealed diverse clusters that were feasible for future structure-activity relationship (SAR) optimization to potent IP6K inhibitors. Medicinal chemistry SAR efforts in three chemical series identified potent IP6K1 inhibitors which were further validated in an orthogonal LC-MS IP7 analysis. The effects of IP6K1 inhibitors on cellular IP7 levels were further confirmed and were found to correlate with cellular IP6K1 binding measured by a high-throughput cellular thermal shift assay (CETSA).
Identifiers
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Registered trials
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.