ArticleProceedings of the National Academy of Sciences of the United States of America2010
Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 135 citations in OpenAlex.
- Review
- Afuresertib plus fulvestrant for pretreated HR-positive, HER2-negative, advanced breast cancer: a phase Ib trial.Nature communications · 2026Article
- Article
- Discovery, Optimization, and Anticancer Activity of Lipid-Competitive Pleckstrin Homology Domain-Containing Family A Inhibitors.Journal of medicinal chemistry · 2025Article
- PRKD2 as a novel target for targeting the diabetes-osteoporosis nexus.Scientific reports · 2025Article
- Bruton's Tyrosine Kinase Inhibitors: A Versatile Therapeutic Approach for Cancer, Autoimmune Disorders, GVHD and COVID-19.Mini reviews in medicinal chemistry · 2025Review
- Small Molecule Modulator of the mTORC2 Pathway Discovered from a DEL Library Designed to Bind to Pleckstrin Homology Domains.ACS chemical biology · 2024Article
- Cell-Permeable Fluorescent Sensors Enable Rapid Live Cell Visualization of Plasma Membrane and Nuclear PIP3 Pools.JACS Au · 2024Article
- Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.Cellular and molecular life sciences : CMLS · 2024Article
- New drug-like small molecule antagonizes phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in patients with conotruncal heart defects.Journal of Taibah University Medical Sciences · 2023Article
- ACKnowledging the role of the Activated-Cdc42 associated kinase (ACK) in regulating protein stability in cancer.Small GTPases · 2023Review
- Stimulus-Controlled Anion Binding and Transport by Synthetic Receptors.Chemical reviews · 2023Review
- Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.Journal of oncology · 2023Article
- LINC01468 drives NAFLD-HCC progression through CUL4A-linked degradation of SHIP2.Cell death discovery · 2022Article
- The role of miR-153 and related upstream/downstream pathways in cancers: from a potential biomarker to treatment of tumor resistance and a therapeutic target.Medical oncology (Northwood, London, England) · 2022Review
- Lipid Profiles of RAS Nanoclusters Regulate RAS Function.Biomolecules · 2021Review
- Mechanisms of Resistance to PI3K Inhibitors in Cancer: Adaptive Responses, Drug Tolerance and Cellular Plasticity.Cancers · 2021Review
- STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia.Frontiers in cell and developmental biology · 2021Article
- "Modulating Phosphoinositide Profiles as a Roadmap for Treatment in Acute Myeloid Leukemia".Frontiers in oncology · 2021Review
- Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4.Nature cell biology · 2020Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3-PH domain interactions (IC(50) ranges from 13.4 to 31 μM in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling.
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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.