ArticleCell chemical biology2019
What Makes a Kinase Promiscuous for Inhibitors?
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 60 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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Who cites it
60 citing papers in PubMed, 106 citations in OpenAlex.
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- Quantum Reactivity-Guided Optimization of ATP-Competitive Ligands through Multiscale Simulation.ACS physical chemistry Au · 2026Article
- Quantification of Binding of Small Molecules to Native Kinases by Flow Cytometry Reveals Divergence from Biochemical Affinities.Journal of the American Chemical Society · 2026Article
- Predicting Clinical Sensitivities of PDGFRA Exon 18 Mutations to Imatinib and Avapritinib to Optimize Gastrointestinal Stromal Tumor Treatment.Cancer research communications · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- Polypharmacology is an enduring and nearly universal property of kinase inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Cellular Context Influences Kinase Inhibitor Selectivity.Journal of medicinal chemistry · 2026Article
- Discovery of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRK/PTK6 inhibitors.European journal of medicinal chemistry · 2025Article
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- Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.The journal of physical chemistry. B · 2025Article
- Prospective evaluation of structure-based simulations reveal their ability to predict the impact of kinase mutations on inhibitor binding.bioRxiv : the preprint server for biology · 2025Article
- Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Recognizing and Managing Breast Implant Complications: A Review for Healthcare Providers Who Treat Women Who Underwent Breast Implant-Based Surgery.International journal of women's health · 2025Review
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- Comprehensive detection and characterization of human druggable pockets through binding site descriptors.Nature communications · 2024Article
- Light-gated integrator for highlighting kinase activity in living cells.Nature communications · 2024Article
- Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE.eLife · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
ATP-competitive kinase inhibitors often bind several kinases due to the high conservation of the ATP binding pocket. Through clustering analysis of a large kinome profiling dataset, we found a cluster of eight promiscuous kinases that on average bind more than five times more kinase inhibitors than the other 398 kinases in the dataset. To understand the structural basis of promiscuous inhibitor binding, we determined the co-crystal structure of the receptor tyrosine kinase DDR1 with the type I inhibitors dasatinib and VX-680. Surprisingly, we find that DDR1 binds these type I inhibitors in an inactive conformation typically reserved for type II inhibitors. Our computational and biochemical studies show that DDR1 is unusually stable in this inactive conformation, giving a mechanistic explanation for inhibitor promiscuity. This phenotypic clustering analysis provides a strategy to obtain functional insights not available by sequence comparison alone.
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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.