ArticleNature2010
Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 305 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
305 citing papers in PubMed.
- Trial
- A design approach for bitopic kinase inhibitors.Nature · 2026Article
- Bend and Snap: Computationally Exploring the Helix Bias for Classifying Abl Kinase Allosteric Modulators.Journal of chemical information and modeling · 2026Article
- Decoding the allosteric grammar of protein kinases: A dual-stream framework integrating protein language models and energy landscape frustration analysis.Protein science : a publication of the Protein Society · 2026Article
- Dual functional genomics reveals a broad and convergent landscape of asciminib resistance in BCR::ABL1.Genome medicine · 2026Article
- Reconsidering dualTranslational cancer research · 2026Article
- Enabling Automatic Generation of Protein-Ligand Complex Data Sets with Atomistic Detail.Journal of chemical information and modeling · 2026Article
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- New selective and allosteric FLT3 inhibitors show efficacy against resistant acute myeloid leukemia cells.iScience · 2026Article
- The allosteric landscape of the Src kinase.Science advances · 2026Article
- RAF isoform selectivity of MEK inhibitors and rational design of a covalent ARAF-MEK inhibitor.bioRxiv : the preprint server for biology · 2025Article
- Selective Identification of Allosteric Inhibitors and Co-Drug Combinations Targeting Kinases by Using a Nanopore Tweezer Approach.ACS nano · 2025Article
- Autophosphorylation of oncoprotein TEL-ABL in myeloid and lymphoid cells confers resistance to the allosteric ABL inhibitor asciminib.Science signaling · 2025Article
- A general assay platform to study protein pharmacology using ligand-dependent structural dynamics.Nature communications · 2025Article
- KinaseFusionDB: an integrative knowledge of kinase fusion proteins in multi-scales.Briefings in bioinformatics · 2025Article
- Advances in reversible covalent kinase inhibitors.Medicinal research reviews · 2025Review
- Asciminib in the treatment of chronic myeloid leukemia in chronic phase.Future oncology (London, England) · 2025Review
- Review
- Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia.Blood · 2025Article
245 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors.
Funding
Abstract
In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
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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.