ArticleThe Journal of biological chemistry2012
The R1275Q neuroblastoma mutant and certain ATP-competitive inhibitors stabilize alternative activation loop conformations of anaplastic lymphoma kinase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 49 citations in OpenAlex.
- A structure-based virtual screening approach to identify novel anaplastic lymphoma kinase inhibitors.Journal of molecular modeling · 2026Article
- Virtual screening and MD simulation-guided discovery of CDK12-IN-3, a potent ALK inhibitor suppressing neuroblastoma growthFrontiers in chemistry · 2026Article
- Article
- AnFrontiers in pharmacology · 2025Article
- Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma.Nature communications · 2023Article
- Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs.International journal of molecular sciences · 2023Review
- Engineered PROTAC-CID Systems for Mammalian Inducible Gene Regulation.Journal of the American Chemical Society · 2023Article
- ALK F1174S mutation impairs ALK kinase activity in EML4-ALK variant 1 and sensitizes EML4-ALK variant 3 to crizotinib.Frontiers in oncology · 2023Article
- Phase-separated foci of EML4-ALK facilitate signalling and depend upon an active kinase conformation.EMBO reports · 2021Article
- Therapeutic Targeting of the Anaplastic Lymphoma Kinase (ALK) in Neuroblastoma-A Comprehensive Update.Pharmaceutics · 2021Review
- Genome instability and lymphoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics.Journal of computer-aided molecular design · 2020Article
- Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase: A Catalytic Receptor with Many Faces.International journal of molecular sciences · 2018Review
- Reviving B-Factors: Activating ALK Mutations Increase Protein Dynamics of the Unphosphorylated Kinase.ACS medicinal chemistry letters · 2018Article
- Molecular Modeling for Structural Insights Concerning the Activation Mechanisms of F1174L and R1275Q Mutations on Anaplastic Lymphoma Kinase.Molecules (Basel, Switzerland) · 2018Article
- Review
- A Computational Approach for Prioritizing Selection of Therapies Targeting Drug Resistant Variation in Anaplastic Lymphoma Kinase.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2018Article
- Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets.Pathology oncology research : POR · 2017Article
- Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB.Frontiers in molecular neuroscience · 2017Article
- Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that, when genetically altered by mutation, amplification, chromosomal translocation or inversion, has been shown to play an oncogenic role in certain cancers. Small molecule inhibitors targeting the kinase activity of ALK have proven to be effective therapies in certain ALK-driven malignancies and one such inhibitor, crizotinib, is now approved for the treatment of EML4-ALK-driven, non-small cell lung cancer. In neuroblastoma, activating point mutations in the ALK kinase domain can drive disease progression, with the two most common mutations being F1174L and R1275Q. We report here crystal structures of the ALK kinase domain containing the F1174L and R1275Q mutations. Also included are crystal structures of ALK in complex with novel small molecule ALK inhibitors, including a classic type II inhibitor, that stabilize previously unobserved conformations of the ALK activation loop. Collectively, these structures illustrate a different series of activation loop conformations than has been observed in previous ALK crystal structures and provide insight into the activating nature of the R1275Q mutation. The novel active site topologies presented here may also aid the structure-based drug design of a new generation of ALK inhibitors.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.