ArticleCell chemical biology2019
Differences in the Conformational Energy Landscape of CDK1 and CDK2 Suggest a Mechanism for Achieving Selective CDK Inhibition.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 143 citations in OpenAlex.
- The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.The Biochemical journal · 2026Article
- Structural insights into multitargetingMicrobiology spectrum · 2026Article
- Proposed Allosteric Inhibition of Cyclin-Dependent Kinase 4 by a Proline-Derived Acylsemicarbazide Compound with Antiproliferative Activity in Breast Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Evaluation of the Anti-Cancer Effects of KMU-11342 in In Vitro and Ex Vivo Models of Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Contact-Network Phenotyping of the CDK Family Reveals Selective Distal C-Lobe Contact Redistribution by Modern CDK5 Inhibitors and a Quantitative Selectivity Landscape against CDK2 and CDK1.Journal of chemical information and modeling · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- New predicted dual CDK-2/CDK-1 inhibitors from Aspergillus unguis isolate SP51-EGY with relative selectivity for colorectal cancer cells: a computational and experimental approach.Scientific reports · 2026Article
- Novel indole-based scaffolds: Design, synthesis, molecular modeling, and anti-proliferative evaluation.BMC chemistry · 2026Article
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- In Silico Identification of Hydroxyxanthone Derivatives as CDK2/EGFR Dual Inhibitor for Colorectal Cancer Treatment.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16.Nature communications · 2026Article
- Synthesis, characterization, DFT analysis, molecular docking and anticancer investigations in colorectal carcinoma of a novel pyrazole-hydrazone zinc(II) complex.Scientific reports · 2026Article
- CDK1 Signaling in Cancer Treatment: Advances in AI-based Strategies and Tools for New Cancer Drug Discovery.Combinatorial chemistry & high throughput screening · 2026Article
- Multi-omics pan-cancer profiling of CDK2 andRSC advances · 2025Article
- From Mushrooms to Molecules: Exploring Depsidones inMolecules (Basel, Switzerland) · 2025Article
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- Total Synthesis of Rohitukine and Dysoline and Their Anticancer Analogues Flavopiridol and IIIM-290.ACS omega · 2025Article
- From cell cycle control to cancer therapy: exploring the role of CDK1 and CDK2 in tumorigenesis.Medical oncology (Northwood, London, England) · 2025Review
- Machine Learning Meets Physics-based Modeling: A Mass-spring System to Predict Protein-ligand Binding Affinity.Current medicinal chemistry · 2025Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of the cell cycle characterizes many cancer subtypes, providing a rationale for developing cyclin-dependent kinase (CDK) inhibitors. Potent CDK2 inhibitors might target certain cancers in which CCNE1 is amplified. However, current CDK2 inhibitors also inhibit CDK1, generating a toxicity liability. We have used biophysical measurements and X-ray crystallography to investigate the ATP-competitive inhibitor binding properties of cyclin-free and cyclin-bound CDK1 and CDK2. We show that these kinases can readily be distinguished by such inhibitors when cyclin-free, but not when cyclin-bound. The basis for this discrimination is unclear from either inspection or molecular dynamics simulation of ligand-bound CDKs, but is reflected in the contacts made between the kinase N- and C-lobes. We conclude that there is a subtle but profound difference between the conformational energy landscapes of cyclin-free CDK1 and CDK2. The unusual properties of CDK1 might be exploited to differentiate CDK1 from other CDKs in future cancer therapeutic design.
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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.