ArticleFrontiers in immunology2014
Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.
Article in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- The conformation-selective PI3Kδ inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial.Nature communications · 2026Article
- The PI3Kδ inhibitor roginolisib (IOA-244) preserves T-cell function and activity.Molecular oncology · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- From the gene to the clinic: Key milestones in the PI3Kδ journey.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Defining PI3K Signaling as a Key Regulator of Molecular Heterogeneity and Inflammation in Glomerular Lupus Nephritis.Immune network · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- Roginolisib in Combination with JAK Inhibitors in Patients with Myelofibrosis Who are Unresponsive to Approved JAK Inhibitors (Study HEMA-MED) - A Trial in Progress.OncoTargets and therapy · 2026Article
- Transforming lupus self-care education with mobile health: A systematic review.Journal of education and health promotion · 2026Review
- Phosphoinositide 3-kinase δ activity in patients with systemic lupus erythematosus.Frontiers in immunology · 2026Article
- Article
- Novel PI3kδ inhibitor roginolisib synergizes with venetoclax in hematologic malignancies.Haematologica · 2025Article
- Targeting T regulatory (TCancer drug resistance (Alhambra, Calif.) · 2024Review
- Non-Clinical Toxicology Evaluation of the Novel Non-ATP Competitive Oral PI3 Kinase Delta Inhibitor Roginolisib.International journal of toxicology · 2023Article
- Tuning the Biological Activity of PI3KMolecules (Basel, Switzerland) · 2023Article
- IOA-244 is a Non-ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance.Cancer research communications · 2023Article
- Dual inhibition of phosphoinositide 3-kinases delta and gamma reduces chronic B cell activation and autoantibody production in a mouse model of lupus.Frontiers in immunology · 2023Article
- Chlorogenic Acid Relieves the Lupus Erythematosus-like Skin Lesions and Arthritis in MRL/lpr Mice.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Design, Synthesis, and Development of pyrazolo[1,5-Pharmaceuticals (Basel, Switzerland) · 2022Article
- Design, Synthesis, and Development of Pyrazolo[1,5-Pharmaceuticals (Basel, Switzerland) · 2022Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.
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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.