ArticleProceedings of the National Academy of Sciences of the United States of America2007
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.
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
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 375 citations in OpenAlex.
- A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors.Marine drugs · 2019Pooled it
- A Hanks-type bacterial kinase, PknS, directly phosphorylates the alternative sigma factor EcfK to promote resistance to protist predation.The FEBS journal · 2026Article
- Reflectometric-based sensor arrays for the screening of kinase-inhibitor interactions and kinetic determination.Analytical and bioanalytical chemistry · 2025Article
- Penetrant PKCβ mutation in ATLL displays a mixed gain-of-function.The Biochemical journal · 2025Article
- Haspin kinase binds to a nucleosomal DNA supergroove.Nature structural & molecular biology · 2025Article
- Pharmacophore Modeling of Janus Kinase Inhibitors: Tools for Drug Discovery and Exposition Prediction.Molecules (Basel, Switzerland) · 2025Article
- Workflow for E3 Ligase Ligand Validation for PROTAC Development.ACS chemical biology · 2025Article
- Differential scanning fluorimetry followed by microscale thermophoresis and/or isothermal titration calorimetry as an efficient tool for ligand screening.Biophysical reviews · 2025Review
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Identification and structural characterization of small molecule inhibitors of PINK1.Scientific reports · 2024Article
- Activating mutations drive human MEK1 kinase using a gear-shifting mechanism.The Biochemical journal · 2023Article
- Bisindolyl Maleimides and Indolylmaleimide Derivatives-A Review of Their Synthesis and Bioactivity.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor.Aging cell · 2023Article
- Article
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
- Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective.ACS chemical neuroscience · 2023Article
- Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.Scientific reports · 2023Article
- VRK1 Kinase Activity Modulating Histone H4K16 Acetylation Inhibited by SIRT2 and VRK-IN-1.International journal of molecular sciences · 2023Article
- A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective.bioRxiv : the preprint server for biology · 2023Article
- Pharmacological approaches to understanding protein kinase signaling networks.Frontiers in pharmacology · 2023Review
91 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
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein kinases play a pivotal role in cell signaling, and dysregulation of many kinases has been linked to disease development. A large number of kinase inhibitors are therefore currently under investigation in clinical trials, and so far seven inhibitors have been approved as anti-cancer drugs. In addition, kinase inhibitors are widely used as specific probes to study cell signaling, but systematic studies describing selectivity of these reagents across a panel of diverse kinases are largely lacking. Here we evaluated the specificity of 156 validated kinase inhibitors, including inhibitors used in clinical trials, against 60 human Ser/Thr kinases using a thermal stability shift assay. Our analysis revealed many unexpected cross-reactivities for inhibitors thought to be specific for certain targets. We also found that certain combinations of active-site residues in the ATP-binding site correlated with the detected ligand promiscuity and that some kinases are highly sensitive to inhibition using diverse chemotypes, suggesting them as preferred intervention points. Our results uncovered also inhibitor cross-reactivities that may lead to alternate clinical applications. For example, LY333'531, a PKCbeta inhibitor currently in phase III clinical trials, efficiently inhibited PIM1 kinase in our screen, a suggested target for treatment of leukemia. We determined the binding mode of this inhibitor by x-ray crystallography and in addition showed that LY333'531 induced cell death and significantly suppressed growth of leukemic cells from acute myeloid leukemia patients.
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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.