ArticleCancer research2009
The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Tyrosine kinase inhibitors as an alternative treatment in canine mast cell tumor.Frontiers in veterinary science · 2023Pooled it
- The cyclin dependent kinase (CDK)7 inhibitor BS-181 inhibits pathogenic Cryptococcus species, causing GVirulence · 2026Article
- Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms.Medicinal research reviews · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.Cell death & disease · 2026Article
- Synthesis, Spectroscopic, Electronic and Molecular Docking Studies of Pyrazole Based Chalcones as Potential Anticancer Agents.Journal of fluorescence · 2025Article
- Transcriptome-conditioned molecule generation via gene interaction-aware fragment modeling with a GPT-based architecture.Scientific reports · 2025Article
- Recent advances in development of CDK7 inhibitors and their clinical trials: a narrative review.Translational cancer research · 2025Review
- Drug design for cyclin-dependent kinase 9 (CDK9) inhibitorsBiochemistry and biophysics reports · 2025Article
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides.Scientific reports · 2025Article
- PRR11 Promotes Bladder Cancer Growth and Metastasis by Facilitating G1/S Progression and Epithelial-Mesenchymal Transition.Cancer medicine · 2025Article
- Emerging roles of cyclin-dependent kinase 7 in health and diseases.Trends in molecular medicine · 2025Review
- Using bioinformatics and artificial intelligence to map the cyclin-dependent kinase 4/6 inhibitor biomarker landscape in breast cancer.Future oncology (London, England) · 2024Review
- Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).European journal of medicinal chemistry · 2024Article
- Design, Synthesis, and Biological Evaluation of 2,4-Diaminopyrimidine Derivatives as Potent CDK7 Inhibitors.ACS medicinal chemistry letters · 2024Article
- Cimicifugin, a broad-spectrum inhibitor ofAntimicrobial agents and chemotherapy · 2024Article
- Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.International journal of molecular sciences · 2024Article
- Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.British journal of cancer · 2024Review
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Normal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. Direct or indirect deregulation of CDK activity is a feature of almost all cancers and has led to the development of CDK inhibitors as anticancer agents. The CDK-activating kinase (CAK) plays a critical role in regulating cell cycle by mediating the activating phosphorylation of CDK1, CDK2, CDK4, and CDK6. As such, CDK7, which also regulates transcription as part of the TFIIH basal transcription factor, is an attractive target for the development of anticancer drugs. Computer modeling of the CDK7 structure was used to design potential potent CDK7 inhibitors. Here, we show that a pyrazolo[1,5-a]pyrimidine-derived compound, BS-181, inhibited CAK activity with an IC(50) of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 micromol/L, with CDK2 being inhibited 35-fold less potently (IC(50) 880 nmol/L) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines, and showed antitumor effects in vivo. The drug was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of drug inhibited the growth of MCF-7 human xenografts in nude mice. BS-181 therefore provides the first example of a potent and selective CDK7 inhibitor with potential as an anticancer agent.
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What OpenQuestion holds
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.