ArticleBriefings in bioinformatics2021
Landscape of drug-resistance mutations in kinase regulatory hotspots.
Article in Briefings in bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Multi-omic integration identifies broad drug resistance mechanisms and strategies to therapeutically reprogram cancer cells.iScience · 2026Article
- Dr. Kinase: predicting the drug-resistance hotspots of protein kinases.Nucleic acids research · 2025Article
- Overcoming Secondary Mutations of Type II Kinase Inhibitors.Journal of medicinal chemistry · 2024Review
- Unraveling Extremely DamagingJournal of personalized medicine · 2023Article
- Prediction of Amino Acid Substitutions in ABL1 Protein Leading to Tumor Drug Resistance Based on "Structure-Property" Relationship Classification Models.Life (Basel, Switzerland) · 2023Article
- Arf GTPase activates the WAVE regulatory complex through a distinct binding site.Science advances · 2022Article
- Predicting the mutation effects of protein-ligand interactions via end-point binding free energy calculations: strategies and analyses.Journal of cheminformatics · 2022Article
- Regulatory spine RS3 residue of protein kinases: a lipophilic bystander or a decisive element in the small-molecule kinase inhibitor binding?Biochemical Society transactions · 2022Article
- The protein kinase CK1: Inhibition, activation, and possible allosteric modulation.Frontiers in molecular biosciences · 2022Review
- Anti-neoplastic characteristics and potential targets of calycosin against bisphenol A-related osteosarcoma: bioinformatics analysis.Bioengineered · 2021Article
- KinaseMD: kinase mutations and drug response database.Nucleic acids research · 2021Article
- Structure-guided machine learning prediction of drug resistance mutations in Abelson 1 kinase.Computational and structural biotechnology journal · 2021Article
- Transmembrane Polar Relay Drives the Allosteric Regulation for ABCG5/G8 Sterol Transporter.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
More than 48 kinase inhibitors (KIs) have been approved by Food and Drug Administration. However, drug-resistance (DR) eventually occurs, and secondary mutations have been found in the previously targeted primary-mutated cancer cells. Cancer and drug research communities recognize the importance of the kinase domain (KD) mutations for kinasopathies. So far, a systematic investigation of kinase mutations on DR hotspots has not been done yet. In this study, we systematically investigated four types of representative mutation hotspots (gatekeeper, G-loop, αC-helix and A-loop) associated with DR in 538 human protein kinases using large-scale cancer data sets (TCGA, ICGC, COSMIC and GDSC). Our results revealed 358 kinases harboring 3318 mutations that covered 702 drug resistance hotspot residues. Among them, 197 kinases had multiple genetic variants on each residue. We further computationally assessed and validated the epidermal growth factor receptor mutations on protein structure and drug-binding efficacy. This is the first study to provide a landscape view of DR-associated mutation hotspots in kinase's secondary structures, and its knowledge will help the development of effective next-generation KIs for better precision medicine.
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