ArticleCancer research2013
PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 245 citations in OpenAlex.
- Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.Nature communications · 2026Article
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- The Chromatin Remodeler Chd8 Regulates Hematopoietic Stem and Progenitor Cell Survival and Differentiation During Zebrafish Embryogenesis.International journal of molecular sciences · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Tyr1497 in the BRG1 Bromodomain of the SWI/SNF Complex is Critical for the Binding and Function of a Selective BRG1 Inhibitor.Journal of cellular and molecular medicine · 2025Article
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- Docking‑based virtual screening of BRD4 (BD1) inhibitors: assessment of docking methods, scoring functions and in silico molecular properties.BMC chemistry · 2024Article
- JK-1, a useful erythroleukemic cell line model to study a controlled erythroid differentiation from progenitors to terminal erythropoiesis.Scientific reports · 2024Article
- Combining Data-Driven and Structure-Based Approaches in Designing Dual PARP1-BRD4 Inhibitors for Breast Cancer Treatment.Journal of chemical information and modeling · 2024Article
- Epigenetic modulation through BET bromodomain inhibitors as a novel therapeutic strategy for progranulin-deficient frontotemporal dementia.Scientific reports · 2024Article
- Article
- Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.Epigenomes · 2024Review
- Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1.Theranostics · 2024Article
- Epigenetic Modulators as Therapeutic Agents in Cancer.International journal of molecular sciences · 2023Review
- Next-generation bromodomain inhibitors of the SWI/SNF complex enhance DNA damage and cell death in glioblastoma.Journal of cellular and molecular medicine · 2023Article
- CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Novel Approaches for the Solid-Phase Synthesis of Dihydroquinazoline-2(1Molecules (Basel, Switzerland) · 2022Article
- Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection.Microbiology spectrum · 2022Article
- Roles of Bromodomain Extra Terminal Proteins in Metabolic Signaling and Diseases.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Development of BRD4 inhibitors as anti-inflammatory agents and antidotes for arsenicals.Bioorganic & medicinal chemistry letters · 2022Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. BET proteins are recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 and H4. Inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer. Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target.
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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.