ArticleOncogene2018
The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02516553 (An Open Label, Phase Ia/Ib Dose Finding Study With BI 894999 Orally Administered Once a Day in Patients With Advanced Malignancies, With Repeated Administration in Patients With Clinical Benefit), which is not on this map. Cited by 57 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.
An Open Label, Phase Ia/Ib Dose Finding Study With BI 894999 Orally Administered Once a Day in Patients With Advanced Malignancies, With Repeated Administration in Patients With Clinical Benefit
Who cites it
57 citing papers in PubMed, 82 citations in OpenAlex.
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- Epigenetic Targeting in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models.Cell reports. Medicine · 2025Article
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Super-enhancers in hepatocellular carcinoma: regulatory mechanism and therapeutic targets.Cancer cell international · 2025Review
- Core transcriptional regulatory circuitry molecule ZNF217 promotes AML cell proliferation by up-regulating MYB.International journal of biological sciences · 2025Article
- Super enhancers as key drivers of gene regulatory networks in normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2025Review
- MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.Aging and disease · 2024Review
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling.Experimental hematology & oncology · 2024Article
- Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.Cancer metastasis reviews · 2024Review
- Article
- Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine.Scientific reports · 2023Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Analysis of super-enhancer using machine learning and its application to medical biology.Briefings in bioinformatics · 2023Review
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- Super enhancers: Pathogenic roles and potential therapeutic targets for acute myeloid leukemia (AML).Genes & diseases · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bromodomain and extra-terminal (BET) protein inhibitors have been reported as treatment options for acute myeloid leukemia (AML) in preclinical models and are currently being evaluated in clinical trials. This work presents a novel potent and selective BET inhibitor (BI 894999), which has recently entered clinical trials (NCT02516553). In preclinical studies, this compound is highly active in AML cell lines, primary patient samples, and xenografts. HEXIM1 is described as an excellent pharmacodynamic biomarker for target engagement in tumors as well as in blood. Mechanistic studies show that BI 894999 targets super-enhancer-regulated oncogenes and other lineage-specific factors, which are involved in the maintenance of the disease state. BI 894999 is active as monotherapy in AML xenografts, and in addition leads to strongly enhanced antitumor effects in combination with CDK9 inhibitors. This treatment combination results in a marked decrease of global p-Ser2 RNA polymerase II levels and leads to rapid induction of apoptosis in vitro and in vivo. Together, these data provide a strong rationale for the clinical evaluation of BI 894999 in AML.
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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.