ArticleOncogene2019
B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Fungal metabolite-based immunotherapy overcomes tumor-associated macrophage immunosuppression.Cell reports. Medicine · 2026Article
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Synthesis and antitumor activity of steroid-based imidazolium salts.RSC advances · 2025Article
- Synthesis and biological activity study of tanshinone I-pyridinium salt derivatives.Natural products and bioprospecting · 2025Article
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials.Stem cell research & therapy · 2025Review
- A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway.Chemical research in toxicology · 2025Article
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence.bioRxiv : the preprint server for biology · 2024Article
- β-carboline derivative Z86 attenuates colorectal cancer cell proliferation and migration by directly targeting PI3K.Natural products and bioprospecting · 2024Article
- Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles.Frontiers in chemistry · 2023Article
- Targeting Breast Cancer Stem Cells.International journal of biological sciences · 2023Review
- Suppressive effects of (-)-tubaic acid on RANKL-induced osteoclast differentiation and bone resorption.Animal cells and systems · 2023Article
- Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance.Frontiers in oncology · 2022Review
- mTOR Inhibition Ablates Cisplatin-Resistant Salivary Gland Cancer Stem Cells.Journal of dental research · 2021Article
- PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.International journal of molecular sciences · 2021Review
- Targeting Phosphatases and Kinases: How to Checkmate Cancer.Frontiers in cell and developmental biology · 2021Review
- miR-7 Reduces Breast Cancer Stem Cell Metastasis via Inhibiting RELA to Decrease ESAM Expression.Molecular therapy oncolytics · 2020Article
- Association between Genetic and Immunological Background of Hepatocellular Carcinoma and Expression of Programmed Cell Death-1.Liver cancer · 2020Article
- Immune Phenotype and Immune Checkpoint Inhibitors for the Treatment of Human Hepatocellular Carcinoma.Cancers · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) have been implicated in metastasis, relapse, and therapeutic resistance of cancer, so successful cancer therapy may therefore require the development of drugs against CSCs or combining anti-CSCs drugs with conventional therapies. The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently activated signaling pathways in human cancer, playing a central role in tumorigenesis as well as the maintenance of CSCs. Here, we designed and identified B591, a dihydrobenzofuran-imidazolium salt, as a novel specific pan-PI3K inhibitor with potent inhibitory activity against class I PI3K isoforms, which showed effective inhibition of cellular PI3K/mTOR signaling pathway and robust antitumor activity in a set of cancer cell lines. Notably, compared with bulk tumor cell populations, B591 exhibited more potency in suppressing CSCs survival and inducing CSCs apoptosis, and presence of B591 effectively eliminated paclitaxel-enriched CSCs. B591 diminished self-renewal capacity and decreased the expression of epithelial-mesenchymal transition (EMT) markers of CSCs. In vivo, B591 preferentially decreased CSCs levels in mouse xenograft model of human breast cancer as evidenced especially by remarkable reduction of tumor-initiating ability. Consistent with the preferential targeting of CSCs, B591 effectively inhibited breast tumor metastasis and delayed tumor regrowth following paclitaxel treatment. Taken together, our findings establish B591, a novel PI3K inhibitor, as a strong candidate for clinical evaluation as a CSCs targeting agent.
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