ArticleAmerican journal of translational research2019
BRD4 degrader ARV-825 produces long-lasting loss of BRD4 protein and exhibits potent efficacy against cholangiocarcinoma cells.
Article in American journal of translational research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting taurine metabolism via PROTAC-mediated SLC6A6 degradation potentiates photodynamic therapy and reverses immunosuppression in cholangiocarcinoma.Journal of nanobiotechnology · 2026Article
- Transcriptomic profiling of epigenetic regulators and metabolic reprogramming in human cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Article
- Targeting BRD4 in gastric cancer: promoting apoptosis and suppressing tumor progression.Frontiers in pharmacology · 2026Article
- Navigating PROTACs in Cancer Therapy: Advancements, Challenges, and Future Horizons.Food science & nutrition · 2025Review
- BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression.Oncogene · 2024Article
- Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases.Journal of advanced research · 2024Review
- Unlocking the Potential of Camel Milk-Derived Exosomes as Novel Delivery Systems: Enhanced Bioavailability of ARV-825 PROTAC for Cancer Therapy.Pharmaceutics · 2024Article
- CRISPR screening identifies BET and mTOR inhibitor synergy in cholangiocarcinoma through serine glycine one carbon.JCI insight · 2024Article
- BRD4 Inhibition as a Strategy to Prolong the Response to Standard of Care in Estrogen Receptor-Positive Breast Cancer.Cancers · 2023Article
- Chemically induced degradation of epigenetic targets.Chemical Society reviews · 2023Review
- PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.Molecules (Basel, Switzerland) · 2023Review
- Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach.ACS chemical biology · 2023Article
- Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- ARV-825 Showed Antitumor Activity against BRD4-NUT Fusion Protein by Targeting the BRD4.Journal of oncology · 2023Article
- BRD4 PROTAC degrader MZ1 exerts anticancer effects in acute myeloid leukemia by targeting c-Myc and ANP32B genes.Cancer biology & therapy · 2022Article
- PROTACs in gastrointestinal cancers.Molecular therapy oncolytics · 2022Review
- Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.Cancer cell international · 2022Review
- Susceptibility of Lung Carcinoma Cells to Nanostructured Lipid Carrier of ARV-825, a BRD4 Degrading Proteolysis Targeting Chimera.Pharmaceutical research · 2022Article
- Bromodomain and extra-terminal inhibitors emerge as potential therapeutic avenues for gastrointestinal cancers.World journal of gastrointestinal oncology · 2022Review
- The BET inhibitor/degrader ARV-825 prolongs the growth arrest response to Fulvestrant + Palbociclib and suppresses proliferative recovery in ER-positive breast cancer.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRD4, a member of the bromodomain and extraterminal domain (BET) family and an important epigenetic reader, has emerged as an attractive oncology target. Cholangiocarcinoma is a lethal neoplasm without approved targeted therapies. BET bromodomain inhibitors have shown promising effects in certain cancers including cholangiocarcinoma. Recently developed BRD4 Proteolysis Targeting Chimera (PROTAC) compounds lead to fast and efficient degradation of BRD4 and provides longer-lasting effect than small molecule BRD4 inhibitors. In this study, we investigated the antitumor effect of a newly developed BRD4 degrader ARV-825 in cholangiocarcinoma. Immunohistochemistry and Western blotting were used to determine the expression level of BRD4. CCK-8 assay and BrdU ELISA assay were used to assess cell proliferation. Caspase 3/7 activity and Annexin V/PI staining were used to assess apoptosis. We demonstrated that BRD4 expression was elevated in cholangiocarcinoma tissues compared to normal bile duct or surrounding normal liver tissues. ARV-825 produced fast and long-lasting loss of BRD4 protein, resulting in more inhibition of CCA cell proliferation and induction of apoptosis than BRD4 inhibitors OTX-015 and JQ1. C-Myc is a well-known downstream target of BRD4. We found that ARV-825 suppressed c-Myc levels more effectively than BRD4 inhibitors. However, ARV-825 did not inhibit c-Myc expression in CCA cells with low basal c-Myc levels. Further analysis showed that ARV-825 significantly upregulated p21 expression and arrested cell cycle progression at G1 phase. In conclusion, BRD4 degrader ARV-825 leads to rapid and sustained degradation of BRD4 and is effective against cholangiocarcinoma.
Indexed as
Identifiers
31632543PMC6789278W2983793926What OpenQuestion holds
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.