ArticleThe Journal of biological chemistry2016
Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 53 citations in OpenAlex.
- From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia.Leukemia · 2026Review
- Utilizing Engineered Monobodies for the Electrochemical Quantification of Lysozyme.Analytical chemistry · 2025Article
- The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives.Journal of molecular biology · 2025Review
- Current and future of targeted therapies against BCR::ABL kinases.Journal of the Egyptian National Cancer Institute · 2025Review
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 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
- Article
- Identification of Inhibitors of the Disease-Associated Protein Phosphatase Scp1 Using Antibody Mimetic Molecules.International journal of molecular sciences · 2024Article
- Conformation state-specific monobodies regulate the functions of flexible proteins through conformation trapping.Protein science : a publication of the Protein Society · 2023Article
- Article
- Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023Article
- Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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
- Monobodies as tool biologics for accelerating target validation and druggable site discovery.RSC medicinal chemistry · 2021Review
- Tuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly.Nature communications · 2021Article
- Driving CARs with alternative navigation tools - the potential of engineered binding scaffolds.The FEBS journal · 2021Review
- Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains.Nature communications · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl.
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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.