ArticleThe Journal of pharmacology and experimental therapeutics2013
The novel anticancer agent JNJ-26854165 induces cell death through inhibition of cholesterol transport and degradation of ABCA1.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Pleuromutilins Suppress Hepatocellular Carcinoma Growth via ABCA1 Inhibition-Induced Cholesterol Accumulation.Cancers · 2026Article
- Oversized cells activate global proteasome-mediated protein degradation to maintain cell size homeostasis.eLife · 2025Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Ferroptosis-Related lncRNAs Act as Novel Prognostic Biomarkers in the Gastric Adenocarcinoma Microenvironment, Immunotherapy, and Chemotherapy.Oxidative medicine and cellular longevity · 2023Article
- Progress in Anticancer Drug Development Targeting Ubiquitination-Related Factors.International journal of molecular sciences · 2022Review
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Strategies to gain novel Alzheimer's disease diagnostics and therapeutics using modulators of ABCA transporters.Free neuropathology · 2021Article
- Combined inhibition of MDM2 and BCR-ABL1 tyrosine kinase targets chronic myeloid leukemia stem/progenitor cells in a murine model.Haematologica · 2020Article
- Role ofJournal of Cancer · 2020Review
- Analysis of Low Molecular Weight Substances and Related Processes Influencing Cellular Cholesterol Efflux.Pharmaceutical medicine · 2019Review
- Review
- The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization.Molecules (Basel, Switzerland) · 2018Article
- An inhibitor of cholesterol absorption displays anti-myeloma activity by targeting the JAK2-STAT3 signaling pathway.Oncotarget · 2016Article
- Review
- The re-emergence of natural products for drug discovery in the genomics era.Nature reviews. Drug discovery · 2015Review
- High Cholesterol Deteriorates Bone Health: New Insights into Molecular Mechanisms.Frontiers in endocrinology · 2015Review
- Understanding drugs in breast cancer through drug sensitivity screening.SpringerPlus · 2015Article
- Article
- Disruption of Lipid Raft Microdomains, Regulation of CD38, TP53, and MYC Signaling, and Induction of Apoptosis by Lomitapide in Multiple Myeloma Cells.Cancer genomics & proteomicsArticle
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
JNJ-26854165 (serdemetan) has previously been reported to inhibit the function of the E3 ligase human double minute 2, and we initially sought to characterize its activity in models of mantle cell lymphoma (MCL) and multiple myeloma (MM). Serdemetan induced a dose-dependent inhibition of proliferation in both wild-type (wt) and mutant (mut) p53 cell lines, with IC50 values from 0.25 to 3 μM/l, in association with an S phase cell cycle arrest. Caspase-3 activation was primarily seen in wtp53-bearing cells but also occurred in mutp53-bearing cells, albeit to a lesser extent. 293T cells treated with JNJ-26854165 and serdemetan-resistant fibroblasts displayed accumulation of cholesterol within endosomes, a phenotype reminiscent of that seen in the ATP-binding cassette subfamily A member-1 (ABCA1) cholesterol transport disorder, Tangiers disease. MM and MCL cells had decreased cholesterol efflux and electron microscopy demonstrated the accumulation of lipid whorls, confirming the lysosomal storage disease phenotype. JNJ-26854165 induced induction of cholesterol regulatory genes, sterol regulatory element-binding transcription factor-1 and -2, liver X receptors α and β, along with increased expression of Niemann-Pick disease type-C1 and -C2. However, JNJ-26854165 induced enhanced ABCA1 turnover despite enhancing transcription. Finally, ABCA1 depletion resulted in enhanced sensitivity to JNJ-26854165. Overall, these findings support the hypothesis that serdemetan functions in part by inhibiting cholesterol transport and that this pathway is a potential new target for the treatment of MCL and MM.
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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.