ArticleCell2011
Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.
Article in Cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed.
- Intracellular protein binders for imaging, control and future therapeutics.Nature biomedical engineering · 2026Review
- From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia.Leukemia · 2026Review
- How I treat Ph+ acute lymphoblastic leukemia.Future oncology (London, England) · 2025Review
- Activity of STAMP inhibitors inBlood neoplasia · 2025Article
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- Generating and validating renewable affimer protein binding reagents targeting SH2 domains.Scientific reports · 2024Article
- Cytosolic delivery of monobodies using the bacterial type III secretion system inhibits oncogenic BCR: ABL1 signaling.Cell communication and signaling : CCS · 2024Article
- Advancements and Future Prospects in Molecular Targeted and siRNA Therapies for Chronic Myeloid Leukemia.Biomolecules · 2024Review
- Improving the pharmacokinetics, biodistribution and plasma stability of monobodies.Frontiers in pharmacology · 2024Article
- Conformation state-specific monobodies regulate the functions of flexible proteins through conformation trapping.Protein science : a publication of the Protein Society · 2023Article
- Article
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Article
- Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Synthesis of the l- and d-SH2 domain of the leukaemia oncogene Bcr-Abl.RSC chemical biology · 2022Article
- Emerging new therapeutic antibody derivatives for cancer treatment.Signal transduction and targeted therapy · 2022Review
- Imatinib can act as an Allosteric Activator of Abl Kinase.Journal of molecular biology · 2022Article
- Allosteric regulation of autoinhibition and activation of c-Abl.Computational and structural biotechnology journal · 2022Article
- Monobodies as tool biologics for accelerating target validation and druggable site discovery.RSC medicinal chemistry · 2021Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention.
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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.