ArticleJournal of molecular biology2022
Imatinib can act as an Allosteric Activator of Abl Kinase.
Article in Journal of molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.International journal of molecular sciences · 2024Pooled it
- 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
- Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.The Journal of biological chemistry · 2026Article
- Expression, purification, and crystallization of recombinant human ABL-1 kinase for X-ray crystallography.Turkish journal of chemistry · 2026Article
- Structure and Dynamics of the ABL1 Tyrosine Kinase and Its Important Role in Chronic Myeloid Leukemia.Archiv der Pharmazie · 2025Review
- Discovery ofMolecules (Basel, Switzerland) · 2025Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- A biophysical framework for double-drugging kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A biophysical framework for double-drugging kinases.bioRxiv : the preprint server for biology · 2023Article
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Mapping the conformational energy landscape of Abl kinase using ClyA nanopore tweezers.Nature communications · 2022Article
- Imatinib disassembles the regulatory core of Abelson kinase by binding to its ATP site and not by binding to its myristoyl pocket.Magnetic resonance (Gottingen, Germany) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Imatinib is an ATP-competitive inhibitor of Bcr-Abl kinase and the first drug approved for chronic myelogenous leukemia (CML) treatment. Here we show that imatinib binds to a secondary, allosteric site located in the myristoyl pocket of Abl to function as an activator of the kinase activity. Abl transitions between an assembled, inhibited state and an extended, activated state. The equilibrium is regulated by the conformation of the αΙ helix, which is located nearby the allosteric pocket. Imatinib binding to the allosteric pocket elicits an αΙ helix conformation that is not compatible with the assembled state, thereby promoting the extended state and stimulating the kinase activity. Although in wild-type Abl the catalytic pocket has a much higher affinity for imatinib than the allosteric pocket does, the two binding affinities are comparable in Abl variants carrying imatinib-resistant mutations in the catalytic site. A previously isolated imatinib-resistant mutation in patients appears to be mediating its function by increasing the affinity of imatinib for the allosteric pocket, providing a hitherto unknown mechanism of drug resistance. Our results highlight the benefit of combining imatinib with allosteric inhibitors to maximize their inhibitory effect on Bcr-Abl.
Indexed as
Identifiers
What Socratic 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 Socratic graph.