ArticleThe Prostate2017
Characterization of a novel p110β-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells.
Article in The Prostate, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- Alternol inhibits GAPDH activity and disrupts glycolytic flux preferentially in cancer cells.Frontiers in pharmacology · 2026Article
- Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death.Frontiers in pharmacology · 2024Article
- Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells.Investigational new drugs · 2023Article
- Hsa_circ_0030586 promotes epithelial-mesenchymal transition in prostate cancer via PI3K-AKT signaling.Bioengineered · 2021Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Construction of enzalutamide-resistant cell model of prostate cancer and preliminary screening of potential drug-resistant genes.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Linc00963 Promote Cell Proliferation and Tumor Growth in Castration-Resistant Prostate Cancer by Modulating miR-655/TRIM24 Axis.Frontiers in oncology · 2021Article
- Overexpression of CXCR7 is a Novel Indicator for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Patients.Disease markers · 2021Article
- Review
- Overcoming the mechanisms of primary and acquired resistance to new generation hormonal therapies in advanced prostate cancer: focus on androgen receptor independent pathways.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Xanthine oxidase-mediated oxidative stress promotes cancer cell-specific apoptosis.Free radical biology & medicine · 2019Article
- Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.The Prostate · 2019Article
- PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling.Endocrinology · 2019Review
- Structural Determinants of Isoform Selectivity in PI3K Inhibitors.Biomolecules · 2019Review
- Enzalutamide-resistant castration-resistant prostate cancer: challenges and solutions.OncoTargets and therapy · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOur previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs. To improve TGX221's aqueous solubility, in this study, we characterized four recently synthesized TGX221 analogs.
methodsTGX221 analog efficacy were examined in multiple prostate cancer cell lines with the SRB cell growth assay, Western blot assay for AKT phosphorylation and cell cycle protein levels. Target engagement with PI3K isoforms was evaluated with cellular thermal shift assay. PI3K activity was determined with the Kinase-Glo Plus luminescent kinase assay. Cell cycle distribution was evaluated with flow cytometry after propidium iodide staining.
resultsAs expected, replacing either one of two major functional groups in TGX221 by more hydrophilic groups dramatically improved the aqueous solubility (about 40-fold) compared to TGX221. In the CETSA assay, all the analogs dramatically shifted the melting curve of p110β protein while none of them largely affected the melting curves of p110α, p110γ, or Akt proteins, indicating target-specific engagement of these analogs with p110β protein. However, functional evaluation showed that only one of the analogs BL140 ubiquitously inhibited AKT phosphorylation in all CRPC cell lines tested with diverse genetic abnormalities including AR, PTEN, and p53 status. BL140 was superior than GSK2636771 (IC
conclusionThese studies suggested that BL140 is a promising p110β-specific inhibitor with multiple superb properties than GSK2636771 worthy for further clinical development.
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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.