ArticleCell death & disease2019
CDK7 inhibitor THZ1 inhibits MCL1 synthesis and drives cholangiocarcinoma apoptosis in combination with BCL2/BCL-XL inhibitor ABT-263.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Discovery of azaindole/indole-fused pyrimidine tetracyclic scaffolds as novel potent CDK7 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- CDK7, CDK9, or CDK11 inhibition reduces neutrophil-driven inflammation and tissue damage in experimental autoimmune models.Cell communication and signaling : CCS · 2026Article
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Pharmacological inhibition of CDK7 and CDK9 suppresses gastrointestinal (colon) cancer progression through modulation of stemness, epithelial-mesenchymal transition, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Drug-tolerant persister cells in lymphoid malignancies: from mechanisms to therapeutic opportunities.Frontiers in oncology · 2026Review
- Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma.Blood neoplasia · 2024Article
- Heparanase interacting BCLAF1 to promote the development and drug resistance of ICC through the PERK/eIF2α pathway.Cancer gene therapy · 2024Article
- Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors.Breast cancer research : BCR · 2023Article
- Article
- CtIP-dependent nascent RNA expression flanking DNA breaks guides the choice of DNA repair pathway.Nature communications · 2022Article
- Blocking CDK7-Mediated NOTCH1-cMYC Signaling Attenuates Cancer Stem Cell Activity in Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2022Article
- Inhibition of MCL1 induces apoptosis in anaplastic large cell lymphoma and in primary effusion lymphoma.Scientific reports · 2022Article
- Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations.Biomedicines · 2021Article
- Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation.Cell death & disease · 2021Article
- Phosphatase PP2A enhances MCL-1 protein half-life in multiple myeloma cells.Cell death & disease · 2021Article
- Expression ofTranslational cancer research · 2021Article
- Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma.Chinese medicine · 2021Article
- CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism.Frontiers in oncology · 2021Article
- Targeting Mutated p53 Dependency in Triple-Negative Breast Cancer Cells Through CDK7 Inhibition.Frontiers in oncology · 2021Article
- Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma.Cancers · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is a fatal disease without effective targeted therapy. We screened a small-molecule library of 116 inhibitors targeting different targets of the cell cycle and discovered several kinases, including Cyclin-dependent kinase 7 (CDK7) as vulnerabilities in CCA. Analysis of multiple CCA data sets demonstrated that CDK7 was overexpressed in CCA tissues. Further studies demonstrated that CDK7 inhibitor THZ1 inhibited cell viability and induced apoptosis in CCA cells. We also showed that THZ1 inhibited CCA cell growth in a xenograft model. RNA-sequencing followed by Gene ontology analysis showed a striking impact of THZ1 on DNA-templated transcriptional programs. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition. A number of oncogenic transcription factors and survival proteins, like MCL1, FOSL1, and RUNX1, were repressed by THZ1. MCL1, one of the antiapoptotic BCL2 family members, was significantly inhibited upon THZ1 treatment. Accordingly, combining THZ1 with a BCL2/BCL-XL inhibitor ABT-263 synergized in impairing cell growth and driving apoptosis. Our results demonstrate CDK7 as a potential target in treating CCA. Combinations of CDK7 inhibition and BCL2/BCL-XL inhibition may offer a novel therapeutic strategy for CCA.
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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 Socratic graph.