The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib
Open accessAbstract
Dasatinib is a small-molecule kinase inhibitor used for the treatment of imatinib-resistant chronic myelogenous leukemia (CML). We have analyzed the kinases targeted by dasatinib by using an unbiased chemical proteomics approach to detect binding proteins directly from lysates of CML cells. Besides Abl and Src kinases, we have identified the Tec kinases Btk and Tec, but not Itk, as major binders of dasatinib. The kinase activity of Btk and Tec, but not of Itk, was inhibited by nanomolar concentrations of dasatinib in vitro and in cultured cells. We identified the gatekeeper residue as the critical determinant of dasatinib susceptibility. Mutation of Thr-474 in Btk to Ile and Thr-442 in Tec to Ile conferred resistance to dasatinib, whereas mutation of the corresponding residue in Itk (Phe-435) to Thr sensitized the otherwise insensitive Itk to dasatinib. The configuration of this residue may be a predictor for dasatinib sensitivity across the kinome. Analysis of mast cells derived from Btk-deficient mice suggested that inhibition of Btk by dasatinib may be responsible for the observed reduction in histamine release upon dasatinib treatment. Furthermore, dasatinib inhibited histamine release in primary human basophils and secretion of proinflammatory cytokines in immune cells. The observed inhibition of Tec kinases by dasatinib predicts immunosuppressive (side) effects of this drug and may offer therapeutic opportunities for inflammatory and immunological disorders.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“whereas dasatinib, a reversible inhibitor of BTK,23 inhibited nonmutant and mutant BTK with similar efficacy.”
From Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib (2014) · cites this paper as [23]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia
Druker, B. J., Guilhot, F., O’Brien, S. G., Gathmann, I., Kantarjian, H. M., Gattermann, N., Deininger, M. W., Silver, R. T., Goldman, J. M., Stone, R. M., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062867 · Cited by 3,516
A small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,923
Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor
Shah, N. P., Tran, C., Lee, F. Y., Chen, P., Norris, D. J., & Sawyers, C. L. (2004) · Science · doi:10.1126/science.1099480 · Cited by 1,804
Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase
Schindler, T. H., Bornmann, W. G., Pellicena, P., Miller, W. T., Clarkson, B., & Kuriyan, J. (2000) · Science · doi:10.1126/science.289.5486.1938 · Cited by 1,785
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
Talpaz, M., Shah, N. P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O'Brien, S., Nicaise, C., Bleickardt, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055229 · Cited by 1,760
Shah, N. P., Nicoll, J. M., Nagar, B., Gorre, M. E., PAQUETTE, R. L., Kuriyan, J., & Sawyers, C. L. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00096-x · Cited by 1,614
Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
Weisberg, E., Manley, P. W., Breitenstein, W., Brüggen, J., Cowan‐Jacob, S. W., Ray, A., Huntly, B. J. P., Fabbro, D., Fendrich, G., Hall–Meyers, E., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.01.007 · Cited by 1,509
Lombardo, L. J., Lee, F. Y., Chen, P., Norris, D. J., Barrish, J. C., Behnia, K., Castaneda, S., Cornelius, L. A. M., Das, J., Doweyko, A. M., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049486a · Cited by 1,303
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Deininger, M. W., Buchdunger, E., & Druker, B. J. (2004) · Blood · doi:10.1182/blood-2004-08-3097 · Cited by 1,269
Buchdunger, E., Zimmermann, J., Mett, H., Meyer, T., Müller, M., Druker, B. J., & Lydon, N. (1996) · PubMed · Cited by 1,057
Research works printed but not linked: 3
- E Buchdunger, J Zimmermann, H Mett, T Meyer, M Muller, BJ Druker, NB Lydon Cancer Res 56, 100–104 (1996).
- B Nagar, WG Bornmann, P Pellicena, T Schindler, DR Veach, WT Miller, B Clarkson, J Kuriyan Cancer Res 62, 4236–4243 (2002).
- M Vihinen, PT Mattsson, CI Smith Front Biosci 5, D917–D928 (2000).
Cited by
Sorted by citations
Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma
Davis, R. E., Ngo, V. N., Lenz, G., Tolar, P., Young, R. M., Romesser, P. B., Kohlhammer, H., Lamy, L., Zhao, H., Yang, Y., et al. (2010) · Nature · doi:10.1038/nature08638 · Cited by 1,651
Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275
Rix, U., Hantschel, O. D., Dürnberger, G., Rix, L. L. R., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., et al. (2007) · Blood · doi:10.1182/blood-2007-07-102061 · Cited by 671
Self-citationTarget profiling of small molecules by chemical proteomics
Rix, U., & Superti‐Furga, G. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.216 · Cited by 585
Self-citationTargeting Bruton's tyrosine kinase in B cell malignancies
Hendriks, R. W., Yuvaraj, S., & Kil, L. P. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3702 · Cited by 580
Metadata
- Authors
- Hantschel, O., Rix, U., Schmidt, U., Bürckstümmer, T., Kneidinger, M., Schütze, G., Colinge, J., Bennett, K. L., Ellmeier, W., Valent, P., & Superti-Furga, G.
- Affiliations
- Austrian Academy of Sciences (AT)
- Medical University of Vienna (AT)
- *Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 19, 1090 Vienna, Austria;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-08-14
- Volume
- 104
- Issue
- 33
- Pages
- 13283-13288
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1940229
- OpenAlex
- W1991795177
- Cited by
- 284
- References
- 38
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 26 · 2014: 24 · 2013: 33 · 2012: 29
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Keywords
- dasatinib, Bruton's tyrosine kinase, Tec kinase, ITK, BCR-ABL tyrosine kinase inhibitors, chronic myeloid leukemia, imatinib resistance, kinase inhibitor binding, gatekeeper mutation, kinase inhibitor resistance, mast cells, histamine release, basophils, inflammatory cytokines, immunosuppression, chemoproteomics
- MeSH terms
- Dasatinib, Animals, Basophils, Enzyme-Linked Immunosorbent Assay, Histamine Release, Humans, Mice, Inbred C57BL, Protein-Tyrosine Kinases, Pyrimidines, Thiazoles, Fusion Proteins, bcr-abl, K562 Cells, U937 Cells, Protein Kinase Inhibitors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
