ArticleCell death & disease2020
The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Knowledge mapping and bibliometric insights of scientific research on targeted protein degradation in oncology.Journal of cancer research and clinical oncology · 2026Review
- Article
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Targeting the Undruggable: Recent Progress in PROTAC-Induced Transcription Factor Degradation.Cancers · 2025Review
- BRD9 promotes the malignant phenotype of thyroid cancer by activating the MAPK/ERK pathway.Anti-cancer drugs · 2025Article
- hnRNPH1: A Multifaceted Regulator in RNA Processing and Disease Pathogenesis.International journal of molecular sciences · 2025Review
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Bromodomain-containing 4 as a therapeutic target in inflammatory bowel diseases and colorectal cancer.Frontiers in pharmacology · 2025Review
- Targeting POLRMT by IMT1 inhibits colorectal cancer cell growth.Cell death & disease · 2024Article
- Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer.Cancer science · 2024Article
- Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.Current topics in medicinal chemistry · 2024Review
- Targeting super-enhancer activity for colorectal cancer therapy.American journal of translational research · 2024Review
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- PROTACs Targeting Epigenetic Proteins.Acta materia medica · 2023Article
- Targeted Protein Degradation: Advances, Challenges, and Prospects for Computational Methods.Journal of chemical information and modeling · 2023Review
- E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage.Journal of neuroinflammation · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A1874 is a novel BRD4-degrading proteolysis targeting chimera (PROTAC). In primary colon cancer cells and established HCT116 cells, A1874 potently inhibited cell viability, proliferation, cell cycle progression, as well as cell migration and invasion. The BRD4-degrading PROTAC was able to induce caspase and apoptosis activation in colon cancer cells. Furthermore, A1874-induced degradation of BRD4 protein and downregulated BRD-dependent genes (c-Myc, Bcl-2, and cyclin D1) in colon cancer cells. Significantly, A1874-induced anti-colon cancer cell activity was more potent than the known BRD4 inhibitors (JQ1, CPI203, and I-BET151). In BRD4-knockout colon cancer cells A1874 remained cytotoxic, indicating the existence of BRD4-independent mechanisms. In addition to BRD4 degradation, A1874 cytotoxicity in colon cancer cells was also associated with p53 protein stabilization and reactive oxygen species production. Importantly, the antioxidant N-acetyl-cysteine and the p53 inhibitor pifithrin-α attenuated A1874-induced cell death and apoptosis in colon cancer cells. In vivo, A1874 oral administration potently inhibited colon cancer xenograft growth in severe combined immuno-deficient mice. BRD4 degradation and p53 protein elevation, as well as apoptosis induction and oxidative stress were detected in A1874-treated colon cancer tissues. Together, A1874 inhibits colon cancer cell growth through both BRD4-dependent and -independent mechanisms.
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