ArticleNature structural & molecular biology2014
Energetic dissection of Gleevec's selectivity toward human tyrosine kinases.
Article in Nature structural & molecular biology, 2014. 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.
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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, 140 citations in OpenAlex.
- Quantification of Binding of Small Molecules to Native Kinases by Flow Cytometry Reveals Divergence from Biochemical Affinities.Journal of the American Chemical Society · 2026Article
- Selective Identification of Allosteric Inhibitors and Co-Drug Combinations Targeting Kinases by Using a Nanopore Tweezer Approach.ACS nano · 2025Article
- Path-Based Nonequilibrium Binding Free Energy Estimation, from Protein-Ligand to RNA-Ligand Binding.Journal of chemical information and modeling · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases.Proteins · 2024Article
- Binding Affinity Determination in Drug Design: Insights from Lock and Key, Induced Fit, Conformational Selection, and Inhibitor Trapping Models.International journal of molecular sciences · 2024Review
- Exploring the conformational landscapes of protein kinases: perspectives from FRET and DEER.Biochemical Society transactions · 2024Review
- A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.Protein science : a publication of the Protein Society · 2024Article
- Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Classifying protein kinase conformations with machine learning.Protein science : a publication of the Protein Society · 2024Article
- Inhibitor Trapping in Kinases.International journal of molecular sciences · 2024Article
- Approximating Projections of Conformational Boltzmann Distributions with AlphaFold2 Predictions: Opportunities and Limitations.Journal of chemical theory and computation · 2024Article
- Substrate-independent activation pathways of the CRISPR-Cas9 HNH nuclease.Biophysical journal · 2023Article
- A Fluorescence-Based Sensor for Calibrated Measurement of Protein Kinase Stability in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- Approximating conformational Boltzmann distributions with AlphaFold2 predictions.bioRxiv : the preprint server for biology · 2023Article
- Segmental Dynamics of Membranous Cholesterol are Coupled.Journal of the American Chemical Society · 2023Article
- Ferrocene modified analogues of imatinib and nilotinib as potent anti-cancer agents.RSC medicinal chemistry · 2023Article
- Structural mechanism of a drug-binding process involving a large conformational change of the protein target.Nature communications · 2023Article
- Protein Flexibility and Dissociation Pathway Differentiation Can Explain Onset of Resistance Mutations in Kinases.Angewandte Chemie (International ed. in English) · 2022Article
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
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinases are obvious drug targets against cancer, owing to their central role in cellular regulation. Since the discovery of Gleevec, a potent and specific inhibitor of Abl kinase, as a highly successful cancer therapeutic, the ability of this drug to distinguish between Abl and other tyrosine kinases such as Src has been intensely investigated but without much success. Using NMR and fast kinetics, we establish a new model that solves this longstanding question of how the two tyrosine kinases adopt almost identical structures when bound to Gleevec but have vastly different affinities. We show that, in contrast to all other proposed models, the origin of Abl's high affinity lies predominantly in a conformational change after binding. An energy landscape providing tight affinity via an induced fit and binding plasticity via a conformational-selection mechanism is likely to be general for many inhibitors.
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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.