ArticleLeukemia2015
The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Trial
- A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL.Oncotarget · 2017Trial
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
- Integrative machine learning-guidedRSC advances · 2025Article
- Review
- IL-27 attenuated macrophage injury and inflammation induced by Mycobacterium tuberculosis by activating autophagy.In vitro cellular & developmental biology. Animal · 2025Article
- Editorial: Repurposing cancer immunotherapies for use in autoimmunity and transplantation.Frontiers in immunology · 2025Article
- Targeted small molecule therapy and inhibitors for lymphoma.Future medicinal chemistry · 2024Review
- B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia.Frontiers in oncology · 2024Review
- Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Xenograft Model.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Development and validation of an UPLC-ESI-MS/MS method for quantification of duvelisib in plasma: application to pharmacokinetic study in rats.RSC advances · 2023Article
- Roles of PI3Kγ and PI3Kδ in mantle cell lymphoma proliferation and migration contributing to efficacy of the PI3Kγ/δ inhibitor duvelisib.Scientific reports · 2023Article
- Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Simultaneous Inhibition of PI3Kgamma and PI3Kdelta Deteriorates T-cell Function With Implications for Chronic Lymphocytic Leukemia.HemaSphere · 2023Article
- Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors.Blood cancer journal · 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
- Design, synthesis, and biological evaluation of new thieno[2,3-Journal of enzyme inhibition and medicinal chemistry · 2022Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The functional relevance of the B-cell receptor (BCR) and the evolution of protein kinases as therapeutic targets have recently shifted the paradigm for treatment of B-cell malignancies. Inhibition of p110δ with idelalisib has shown clinical activity in chronic lymphocytic leukemia (CLL). The dynamic interplay of isoforms p110δ and p110γ in leukocytes support the hypothesis that dual blockade may provide a therapeutic benefit. IPI-145, an oral inhibitor of p110δ and p110γ isoforms, sensitizes BCR-stimulated and/or stromal co-cultured primary CLL cells to apoptosis (median 20%, n=57; P<0.0001) including samples with poor prognostic markers, unmutated IgVH (n=28) and prior treatment (n=15; P<0.0001). IPI-145 potently inhibits the CD40L/IL-2/IL-10 induced proliferation of CLL cells with an IC50 in sub-nanomolar range. A corresponding dose-responsive inhibition of pAKT(Ser473) is observed with an IC50 of 0.36 nM. IPI-145 diminishes the BCR-induced chemokines CCL3 and CCL4 secretion to 17% and 37%, respectively. Pre-treatment with 1 μM IPI-145 inhibits the chemotaxis toward CXCL12; reduces pseudoemperipolesis to median 50%, inferring its ability to interfere with homing capabilities of CLL cells. BCR-activated signaling proteins AKT(Ser473), BAD(Ser112), ERK(Thr202/Tyr204) and S6(Ser235/236) are mitigated by IPI-145. Importantly, for clinical development in hematological malignancies, IPI-145 is selective to CLL B cells, sparing normal B- and T-lymphocytes.
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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.