ReviewJournal of cellular and molecular medicine2010
Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases.
Review in Journal of cellular and molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation.International journal of molecular sciences · 2023Article
- Allosteric regulation and inhibition of protein kinases.Biochemical Society transactions · 2023Review
- Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression?Journal of clinical medicine · 2022Article
- Recent advances in targeting protein kinases and pseudokinases in cancer biology.Frontiers in cell and developmental biology · 2022Review
- Identification of Potent and Selective JAK1 Lead Compounds Through Ligand-Based Drug Design Approaches.Frontiers in pharmacology · 2022Article
- Article
- Are peptides a solution for the treatment of hyperactivated JAK3 pathways?Inflammopharmacology · 2019Review
- Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2019Review
- Hyperactivation of Oncogenic JAK3 Mutants Depend on ATP Binding to the Pseudokinase Domain.Frontiers in oncology · 2018Article
- JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules.ACS medicinal chemistry letters · 2017Article
- Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.Frontiers in endocrinology · 2017Review
- Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.Journal of molecular biology · 2016Article
- The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome.Leukemia · 2016Review
- Article
- Review
- ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The role of the Janus-faced transcription factor PAX5-JAK2 in acute lymphoblastic leukemia.Blood · 2015Article
- JAK2 activation by growth hormone and other cytokines.The Biochemical journal · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gain-of-function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets.
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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.