ArticleeLife2020
Differential impact of BTK active site inhibitors on the conformational state of full-length BTK.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- More than an attachment module: covalent inhibitor warheads influence BTK dynamics and function.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Covalent Ligands with AlphaFold3.Journal of the American Chemical Society · 2026Article
- Exploring pocket-aware inhibitors of BTK kinase by generative deep learning, molecular docking, and molecular dynamics simulations.RSC advances · 2025Article
- A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network.Pharmacology research & perspectives · 2025Article
- BTK inhibitors and next-generation BTK-targeted therapeutics for B-cell malignancies.Archives of pharmacal research · 2025Review
- Bruton's Tyrosine Kinase Inhibitors: A Versatile Therapeutic Approach for Cancer, Autoimmune Disorders, GVHD and COVID-19.Mini reviews in medicinal chemistry · 2025Review
- USP13 mediates resistance to Ibrutinib in diffuse large B-cell lymphoma via augmenting FHL1 stabilization.American journal of cancer research · 2025Article
- Article
- Single molecule tracking based drug screening.Nature communications · 2024Article
- The Evolving Role of Bruton's Tyrosine Kinase Inhibitors in B Cell Lymphomas.International journal of molecular sciences · 2024Review
- Article
- Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling.Molecular cancer therapeutics · 2024Article
- Screening and Characterization of Allosteric Small Molecules Targeting Bruton's Tyrosine Kinase.Biochemistry · 2024Article
- Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL).Genes · 2023Review
- Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor.Blood · 2023Article
- Structural Complementarity of Bruton's Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.PloS one · 2023Article
- The Btk inhibitor AB-95-LH34 potently inhibits atherosclerotic plaque-induced thrombus formation and platelet procoagulant activity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Comparison of Intermolecular Interactions of Irreversible and Reversible Inhibitors with Bruton's Tyrosine Kinase via Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Bruton's tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. Here, we uncover a range of conformational effects in full-length BTK induced by a panel of active site inhibitors, including large-scale shifts in the conformational equilibria of the regulatory domains. Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form. Future development of BTK inhibitors will need to consider long-range allosteric consequences of inhibitor binding, including the emerging application of these BTK inhibitors in treating COVID-19.
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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 Socratic graph.