ArticleHaematologica2025
Novel PI3kδ inhibitor roginolisib synergizes with venetoclax in hematologic malignancies.
Article in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Article
- 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
- Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.Cancer cell international · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
The phosphoinositide 3-kinase (PI3K) pathway remains a potent drug target in hematological malignancies despite the challenges that have affected clinical drug development, particularly unpredictable toxicity, and inherent/acquired drug resistance. Herein, we tested the activity of a novel PI3Kδ selective, non-ATP competitive inhibitor, roginolisib (IOA-244), in hematological malignancies including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). To identify rational actionable combination partners that can be tested in hematologic malignancies, an unbiased pharmacological screening of 474 compounds was carried out in two lymphoma cell lines. We identified BCL2 blockade with venetoclax as synergistically active with roginolisib, a finding confirmed in a broad panel of lymphoma cell lines, DLBCL cell lines and primary CLL samples. We further demonstrate that the sensitizing effects of roginolisib to venetoclax correlate with suppression of downstream PI3K/AKT pathways and alterations in the expression of the apoptotic proteins BIM, mediated through FOXO1 transactivation, and MCL1, with ubiquitination and degradation mediated through GSK3α/β activation. These findings support proof of concept for roginolisib development in hematological malignancies as a single agent or in combination with venetoclax. A clinical trial of roginolisib with venetoclax and an anti-CD20 antibody is initiating in CLL.
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Registered trials
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