ArticleProceedings of the National Academy of Sciences of the United States of America2014
The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 116 citations in OpenAlex.
- xinguangA preliminary characterization of PI4K/PIPK alterations across solid tumors: an exploratory framework for prognostic and therapeutic stratification.Cancer biology & therapy · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.Nature communications · 2026Article
- Brief report: Therapeutic benefit of ISA-2011B in colorectal cancer.Molecular biology reports · 2026Article
- PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Identification of a component of the tubulin poly-glutamylase complex required for phosphoinositide homeostasis and cilium assembly and maintenance.Nature communications · 2026Article
- PIP5K3 upregulation correlates with unfavorable prognosis in patients with nasopharyngeal carcinoma.Histology and histopathology · 2026Article
- Membrane composition-dependent patterning of Rho and F-actin in an artificial cell cortex.Molecular biology of the cell · 2026Article
- Targeting PIP5K ameliorates hepatic cancer by inhibiting PI3K/AKT and the autophagy mechanism and enhancing ROS-mediated apoptosis.Frontiers in pharmacology · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization.bioRxiv : the preprint server for biology · 2025Article
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Stimulus-Transcription Coupling of TRPM3 Channels: A Signaling Pathway from the Plasma Membrane to the Nucleus.Biomolecules · 2025Review
- Emerging oralFrontiers in oral health · 2025Article
- Article
- Signal Transduction of Transient Receptor Potential TRPM8 Channels: Role of PIP5K, Gq-Proteins, and c-Jun.Molecules (Basel, Switzerland) · 2024Article
- Adaptations of membrane trafficking in cancer and tumorigenesis.Journal of cell science · 2024Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy.
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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.