ArticleCell chemical biology2017
Proteome-wide Map of Targets of T790M-EGFR-Directed Covalent Inhibitors.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 100 citations in OpenAlex.
- Dilating the aging clock with light.Innovation (Cambridge (Mass.)) · 2026Review
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Probing the Effect of Protein and Inhibitor Conformational Flexibility on the Reaction of Rocelitinib-Like Covalent Inhibitors of Epidermal Growth Factor Receptor. A Quantum Mechanics/Molecular Mechanics Study.Journal of chemical information and modeling · 2025Article
- Discovery of DCAF16 Binders for Targeted Protein Degradation.ACS chemical biology · 2025Article
- Multi-tiered chemical proteomic maps of tryptoline acrylamide-protein interactions in cancer cells.Nature chemistry · 2024Article
- Non-kinase off-target inhibitory activities of clinically-relevant kinase inhibitors.European journal of medicinal chemistry · 2024Review
- Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.ACS chemical biology · 2024Article
- Chemical Proteomics-Guided Discovery of Covalent Ligands for Cancer Proteins.Annual review of cancer biology · 2024Article
- High-dose short-term osimertinib treatment is effective in patient-derived metastatic colorectal cancer organoids.BJC reports · 2024Article
- A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition.NPJ precision oncology · 2024Article
- Use of pyridazinediones for tuneable and reversible covalent cysteine modification applied to peptides, proteins and hydrogels.Chemical science · 2023Article
- Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics.Acta pharmacologica Sinica · 2023Article
- AzidoTMT Enables Direct Enrichment and Highly Multiplexed Quantitation of Proteome-Wide Functional Residues.Journal of proteome research · 2023Article
- Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception.Molecular and cellular neurosciences · 2023Article
- An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1.British journal of cancer · 2023Article
- Strategies for Competitive Activity-Based Protein Profiling in Small Molecule Inhibitor Discovery and Characterization.Israel journal of chemistry · 2023Article
- Global profiling of AMG510 modified proteins identified tumor suppressor KEAP1 as an off-target.iScience · 2023Article
- Structural elements that enable specificity for mutant EGFR kinase domains with next-generation small-molecule inhibitors.Methods in enzymology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with non-small cell lung cancers that have kinase-activating epidermal growth factor receptor (EGFR) mutations are highly responsive to first- and second-generation EGFR inhibitors. However, these patients often relapse due to a secondary, drug-resistant mutation in EGFR whereby the gatekeeper threonine is converted to methionine (T790M). Several third-generation EGFR inhibitors have been developed that irreversibly inactivate T790M-EGFR while sparing wild-type EGFR, thus reducing epithelium-based toxicities. Using chemical proteomics, we show here that individual T790M-EGFR inhibitors exhibit strikingly distinct off-target profiles in human cells. The FDA-approved drug osimertinib (AZD9291), in particular, was found to covalently modify cathepsins in cell and animal models, which correlated with lysosomal accumulation of the drug. Our findings thus show how chemical proteomics can be used to differentiate covalent kinase inhibitors based on global selectivity profiles in living systems and identify specific off-targets of these inhibitors that may affect drug activity and safety.
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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.