ArticleThe Journal of biological chemistry2015
Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 115 citations in OpenAlex.
- First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2.Clinical and translational science · 2023Trial
- Lack of Electrocardiographic Effects of Deucravacitinib in Healthy Subjects.Clinical pharmacology in drug development · 2022Trial
- Review
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- Envudeucitinib, a Potent, Next-Generation, Allosteric Inhibitor of TYK2: A Narrative Review.Dermatology and therapy · 2026Review
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes.Nature chemical biology · 2025Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Therapeutic Potential of Targeting the JAK/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition.Journal of clinical medicine · 2024Review
- Expanding the ligandable proteome by paralog hopping with covalent probes.bioRxiv : the preprint server for biology · 2024Article
- Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors.Current medicinal chemistry · 2024Review
- Oncogenic TYK2 P760L kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade.Haematologica · 2023Article
- Tyk2 Targeting in Immune-Mediated Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors.Dermatology and therapy · 2023Review
- Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain.Pharmaceuticals (Basel, Switzerland) · 2023Article
- SOCS-JAK-STAT inhibitors and SOCS mimetics as treatment options for autoimmune uveitis, psoriasis, lupus, and autoimmune encephalitis.Frontiers in immunology · 2023Review
- JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.Frontiers in medicine · 2023Review
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Novel TYK2 Inhibitors with anACS medicinal chemistry letters · 2022Article
- Deucravacitinib for the Treatment of Psoriatic Disease.American journal of clinical dermatology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of signal transduction downstream of the IL-23 receptor represents an intriguing approach to the treatment of autoimmunity. Using a chemogenomics approach marrying kinome-wide inhibitory profiles of a compound library with the cellular activity against an IL-23-stimulated transcriptional response in T lymphocytes, a class of inhibitors was identified that bind to and stabilize the pseudokinase domain of the Janus kinase tyrosine kinase 2 (Tyk2), resulting in blockade of receptor-mediated activation of the adjacent catalytic domain. These Tyk2 pseudokinase domain stabilizers were also shown to inhibit Tyk2-dependent signaling through the Type I interferon receptor but not Tyk2-independent signaling and transcriptional cellular assays, including stimulation through the receptors for IL-2 (JAK1- and JAK3-dependent) and thrombopoietin (JAK2-dependent), demonstrating the high functional selectivity of this approach. A crystal structure of the pseudokinase domain liganded with a representative example showed the compound bound to a site analogous to the ATP-binding site in catalytic kinases with features consistent with high ligand selectivity. The results support a model where the pseudokinase domain regulates activation of the catalytic domain by forming receptor-regulated inhibitory interactions. Tyk2 pseudokinase stabilizers, therefore, represent a novel approach to the design of potent and selective agents for the treatment of autoimmunity.
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.