ArticleChemistry & biology2010
Discovery of dual inhibitors of the immune cell PI3Ks p110delta and p110gamma: a prototype for new anti-inflammatory drugs.
Article in Chemistry & biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 82 citations in OpenAlex.
- A subset of neutrophil phagosomes is characterised by pulses of Class I PI3K activity.Disease models & mechanisms · 2025Article
- Enhancing PI3Kγ inhibitor discovery: a machine learning-based virtual screening approach integrating pharmacophores, docking, and molecular descriptors.Molecular diversity · 2025Article
- Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model.Experimental and therapeutic medicine · 2023Article
- Design, Synthesis, and Development of pyrazolo[1,5-Pharmaceuticals (Basel, Switzerland) · 2022Article
- QSAR analysis on a large and diverse set of potent phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors using MLR and ANN methods.Scientific reports · 2022Article
- Discovery of novel selective PI3Kγ inhibitors through combining machine learning-based virtual screening with multiple protein structures and bio-evaluation.Journal of advanced research · 2022Article
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
- [Mechanism of PI3K/AKT/mTOR signaling pathway for mediating anti-inflammatory and anti-oxidant effects of chrysin: a protein microarray-based study].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Herbal Formula SS-1 Increases Tear Secretion for Sjögren's Syndrome.Frontiers in pharmacology · 2021Article
- Immunological characterization of HM5023507, an orally active PI3Kδ/γ inhibitor.Pharmacology research & perspectives · 2020Article
- The Exploration of Chirality for Improved Druggability within the Human Kinome.Journal of medicinal chemistry · 2020Review
- Structural Determinants of Isoform Selectivity in PI3K Inhibitors.Biomolecules · 2019Review
- Article
- Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.Nature communications · 2017Article
- Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ.ACS medicinal chemistry letters · 2016Article
- Discovery of a Series of 5,11-Dihydro-6ACS medicinal chemistry letters · 2016Article
- Different phosphoinositide 3-kinase isoforms mediate carrageenan nociception and inflammation.Pain · 2016Article
- PI3K inhibitors in inflammation, autoimmunity and cancer.Current opinion in pharmacology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
PI3Kdelta and PI3Kgamma regulate immune cell signaling, while the related PI3Kalpha and PI3Kbeta regulate cell survival and metabolism. Selective inhibitors of PI3Kdelta/gamma represent a potential class of anti-inflammatory agents lacking the antiproliferative effects associated with PI3Kalpha/beta inhibition. Here we report the discovery of PI3Kdelta/gamma inhibitors that display up to 1000-fold selectivity over PI3Kalpha/beta and evaluate these compounds in a high-content inflammation assay using mixtures of primary human cells. We find selective inhibition of only PI3Kdelta is weakly anti-inflammatory, but PI3Kdelta/gamma inhibitors show superior inflammatory marker suppression through suppression of lipopolysaccharide-induced TNFalpha production and T cell activation. Moreover, PI3Kdelta/gamma inhibition yields an anti-inflammatory signature distinct from pan-PI3K inhibition and known anti-inflammatory drugs, yet bears striking similarities to glucocorticoid receptor agonists. These results highlight the potential of selectively designing drugs that target kinases with shared biological function.
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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.