ArticleACS chemical biology2011
Discovery of a potential allosteric ligand binding site in CDK2.
Article in ACS chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 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.
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Who cites it
76 citing papers in PubMed, 177 citations in OpenAlex.
- Speak to a Protein: An Interactive Multimodal Co-Scientist for Protein Analysis.Journal of chemical information and modeling · 2026Article
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- An Integrated Computational Workflow for Discovering Alkaloid-Derived Ligands of Cyclin-Dependent Kinase 2.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Directional information flow as a tool for analyzing protein allostery.bioRxiv : the preprint server for biology · 2026Article
- An electron-density point-cloud framework for robust protein-ligand interaction prediction.Nature communications · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Multi-analytical and biological insights into Malcolmia grandiflora Kuntze.Scientific reports · 2026Article
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Molecular dynamics simulations of proteins: an in-depth review of computational strategies, structural insights, and their role in medicinal chemistry and drug development.Biological cybernetics · 2025Review
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- Structure-Based Design of Potent and Selective MerTK Inhibitors by Modulating the Conformation of αC Helix.Journal of medicinal chemistry · 2025Article
- Can Deep Learning Blind Docking Methods be Used to Predict Allosteric Compounds?Journal of chemical information and modeling · 2025Article
- FeatureDock for protein-ligand docking guided by physicochemical feature-based local environment learning using transformer.npj drug discovery · 2025Article
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Article
- Lucidin fromPharmaceuticals (Basel, Switzerland) · 2025Article
- Predicting Inhibition of CDK2 with SAnDReS: The Application of Machine Learning to Navigate the Scoring Function Space.Current medicinal chemistry · 2025Review
- CDK2 Allosteric Modulators: The New Route in the Design of New Drugs as Anticancer and Non-hormonal Contraceptives.Current medicinal chemistry · 2025Review
- Slower CDK4 and faster CDK2 activation in the cell cycle.Structure (London, England : 1993) · 2024Article
16 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclin-dependent kinases (CDKs) are key regulatory enzymes in cell cycle progression and transcription. Aberrant activity of CDKs has been implicated in a number of medical conditions, and numerous small molecule CDK inhibitors have been reported as potential drug leads. However, these inhibitors exclusively bind to the ATP site, which is largely conserved among protein kinases, and clinical trials have not resulted in viable drug candidates, attributed in part to the lack of target selectivity. CDKs are unique among protein kinases, as their functionality strictly depends on association with their partner proteins, the cyclins. In an effort to identify potential target sites for disruption of the CDK-cyclin interaction, we probed the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS) with human CDK2 and cyclin A using fluorescence spectroscopy and protein crystallography. ANS interacts with free CDK2 in a saturation-dependent manner with an apparent K(d) of 37 μM, and cyclin A displaced ANS from CDK2 with an EC(50) value of 0.6 μM. Co-crystal structures with ANS alone and in ternary complex with ATP site-directed inhibitors revealed two ANS molecules bound adjacent to one another, away from the ATP site, in a large pocket that extends from the DFG region above the C-helix. Binding of ANS is accompanied by substantial structural changes in CDK2, resulting in a C-helix conformation that is incompatible for cyclin A association. These findings indicate the potential of the ANS binding pocket as a new target site for allosteric inhibitors disrupting the interaction of CDKs and cyclins.
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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.