ArticlePloS one2023
Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of tirabrutinib monotherapy in relapsed or refractory B-cell lymphomas/leukemia: a meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- Review
- Emerging Role of BTK Inhibitors in Multiple Sclerosis: From Immunobiology to Clinical Translation.Brain sciences · 2026Review
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Fabrication of Second-Generation Acalabrutinib Nanocrystals by Employing the Nano-Edge Method for Improving the Physico-Chemical Properties and Forecasting their In-Silico Pharmacokinetic Behaviour.AAPS PharmSciTech · 2026Article
- Article
- Article
- Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).RSC advances · 2025Review
- Exploring pocket-aware inhibitors of BTK kinase by generative deep learning, molecular docking, and molecular dynamics simulations.RSC advances · 2025Article
- Modulating the Binding Kinetics of Bruton's Tyrosine Kinase Inhibitors through Transition-State Effects.Journal of the American Chemical Society · 2025Article
- BTK inhibitors and next-generation BTK-targeted therapeutics for B-cell malignancies.Archives of pharmacal research · 2025Review
- Proteome selectivity profiling of photoaffinity probes derived from imidazopyrazine-kinase inhibitors.Communications chemistry · 2025Article
- Article
- Pyrazine-based small molecule kinase inhibitors: clinical applications and patent review (2019-2023).Future medicinal chemistry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Bruton's tyrosine kinase (BTK) is the target of the therapeutic agent, Ibrutinib, that treats chronic lymphocyte leukemia (CLL), mantle cell lymphoma (MCL) and other B cell malignancies. Ibrutinib is a first in class, covalent BTK inhibitor that limits B-cell survival and proliferation. Designing new inhibitors of BTK has been an important objective for advancing development of improved therapeutic agents against cancer and autoimmune disorders. Based on the success of Ibrutinib, several second-generation irreversible BTK inhibitors have been developed that exhibit fewer off-target effects. However, the binding-mode and their interaction with Btk have not been experimentally determined and evaluated at atomic resolution. Here we determined the first crystal structure of the BTK kinase domain in complex with acalabrutinib. In addition, we report a structure of the BTK/tirabrutinib complex and compare these structures with previously solved structures. The structures provide insight in the superior selectivity reported for acalabrutinb and guide future BTK inhibitor development.
Indexed as
Identifiers
What OpenQuestion holds
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.