ArticleJournal of medicinal chemistry2015
Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Fusion Molecules Between the STAT5b Inhibitor Stafib-2-CR and a Cereblon Ligand.ChemistryOpen · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- STAT6: Multidimensional analysis from hematopoietic immune regulation to pathogenesis mechanisms and therapeutic targets in hematologic malignancies.Annals of hematology · 2026Review
- SH2Journal of medicinal chemistry · 2026Article
- The Multifaceted Roles of STAT6: Implications for Precision Immunotherapeutics.ImmunoTargets and therapy · 2026Review
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- Turning Off STAT6 with a Targeted Degrader.Journal of medicinal chemistry · 2025Article
- A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo.Nature chemical biology · 2023Article
- STAT6 Blockade AbrogatesFrontiers in immunology · 2022Article
- The role of macrophages during breast cancer development and response to chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Phosphonopeptides containing free phosphonic groups: recent advances.RSC advances · 2020Review
- Cytosolic delivery of peptidic STAT3 SH2 domain inhibitors.Bioorganic & medicinal chemistry · 2020Article
- Phosphotyrosine isosteres: past, present and future.Organic & biomolecular chemistry · 2020Review
- Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein.Journal of medicinal chemistry · 2019Article
- A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo.Cancer cell · 2019Article
- Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins.BMC molecular and cell biology · 2019Article
- Small molecule targeting of the STAT5/6 Src homology 2 (SH2) domains to inhibit allergic airway disease.The Journal of biological chemistry · 2018Article
- Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases.Journal of autoimmunity · 2017Review
- Interferon γ is a STAT1-dependent direct inducer of BCL6 expression in imatinib-treated chronic myeloid leukemia cells.Oncogene · 2017Article
- Rational development of Stafib-2: a selective, nanomolar inhibitor of the transcription factor STAT5b.Scientific reports · 2017Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4Rα bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.
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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.