ArticleOncotarget2014
Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73.
Article in Oncotarget, 2014. 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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The trial behind it
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- CDK9 inhibition inhibits multiple oncogenic transcriptional and epigenetic pathways in prostate cancer.British journal of cancer · 2024Article
- Ultrasound coupled RES-loaded ultrasound microbubble inhibits the proliferation of ovarian cancer cells by expression of long non-coding RNA (lncRNA) involved in apoptosis using real-time PCR.American journal of cancer research · 2023Article
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents.Frontiers in oncology · 2021Review
- Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B.Open life sciences · 2021Article
- Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction.Pharmaceutics · 2020Article
- Epigenetic inhibitors eliminate senescent melanoma BRAFV600E cells that survive long‑term BRAF inhibition.International journal of oncology · 2020Article
- EZH2 inhibitors abrogate upregulation of trimethylation of H3K27 by CDK9 inhibitors and potentiate its activity against diffuse large B-cell lymphoma.Haematologica · 2020Article
- CDKI-73 is a Novel Pharmacological Inhibitor of Rab11 Cargo Delivery and Innate Immune Secretion.Cells · 2020Article
- Article
- CDK9 inhibitor CDKI-73 is synergetic lethal with PARP inhibitor olaparib in BRCA1 wide-type ovarian cancer.American journal of cancer research · 2020Article
- Targeting CDK9 for treatment of colorectal cancer.Molecular oncology · 2019Article
- CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia.Investigational new drugs · 2019Article
- Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in ovarian cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Article
- Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma.Cell reports · 2017Article
- Inhibitors of cyclin-dependent kinases as cancer therapeutics.Pharmacology & therapeutics · 2017Review
- Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of cellular transcription and translation is a fundamental hallmark of cancer. As CDK9 and Mnks play pivotal roles in the regulation of RNA transcription and protein synthesis, respectively, they are important targets for drug development. We herein report the cellular mechanism of a novel CDK9 inhibitor CDKI-73 in an ovarian cancer cell line (A2780). We also used shRNA-mediated CDK9 knockdown to investigate the importance of CDK9 in the maintenance of A2780 cells. This study revealed that CDKI-73 rapidly inhibited cellular CDK9 kinase activity and down-regulated the RNAPII phosphorylation. This subsequently caused a decrease in the eIF4E phosphorylation by blocking Mnk1 kinase activity. Consistently, CDK9 shRNA was also found to down-regulate the Mnk1 expression. Both CDKI-73 and CDK9 shRNA decreased anti-apoptotic proteins Mcl-1 and Bcl-2 and induced apoptosis. The study confirmed that CDK9 is required for cell survival and that ovarian cancer may be susceptible to CDK9 inhibition strategy. The data also implied a role of CDK9 in eIF4E-mediated translational control, suggesting that CDK9 may have important implication in the Mnk-eIF4E axis, the key determinants of PI3K/Akt/mTOR- and Ras/Raf/MAPK-mediated tumorigenic activity. As such, CDK9 inhibitor drug candidate CDKI-73 should have a major impact on these pathways in human cancers.
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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.