way-252623 has been researched along with Glioblastoma* in 3 studies
3 other study(ies) available for way-252623 and Glioblastoma
| Article | Year |
|---|---|
Discovery of new LXRβ agonists as glioblastoma inhibitors.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; Glioblastoma; HEK293 Cells; Humans; Liver X Receptors; Machine Learning; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasms, Experimental; Oxindoles; Pyrrolidines; Spiro Compounds; Structure-Activity Relationship; Tumor Cells, Cultured | 2020 |
Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl-xL inhibition.
Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U- Topics: Animals; Apoptosis; bcl-X Protein; Benzoates; Benzylamines; Carcinoma; Cell Proliferation; Cell Respiration; Disease Models, Animal; Gene Expression Profiling; Glioblastoma; Humans; Indazoles; Liver X Receptors; Melanoma; Metabolomics; Models, Theoretical; Treatment Outcome | 2019 |
An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers.
Small-molecule inhibitors targeting growth factor receptors have failed to show efficacy for brain cancers, potentially due to their inability to achieve sufficient drug levels in the CNS. Targeting non-oncogene tumor co-dependencies provides an alternative approach, particularly if drugs with high brain penetration can be identified. Here we demonstrate that the highly lethal brain cancer glioblastoma (GBM) is remarkably dependent on cholesterol for survival, rendering these tumors sensitive to Liver X receptor (LXR) agonist-dependent cell death. We show that LXR-623, a clinically viable, highly brain-penetrant LXRα-partial/LXRβ-full agonist selectively kills GBM cells in an LXRβ- and cholesterol-dependent fashion, causing tumor regression and prolonged survival in mouse models. Thus, a metabolic co-dependency provides a pharmacological means to kill growth factor-activated cancers in the CNS. Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cholesterol; Female; Glioblastoma; Humans; Indazoles; Liver X Receptors; Mice; Treatment Outcome | 2016 |