ArticleAngewandte Chemie (International ed. in English)2015
Nanomolar inhibitors of the transcription factor STAT5b with high selectivity over STAT5a.
Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- Stafib-2-CR: an Improved Nanomolar and Selective Inhibitor of the Transcription Factor STAT5b Developed by Conformational Restriction of Stafib-2.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- 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
- SH2Journal of medicinal chemistry · 2026Article
- Activity Analysis of the P2X Receptor Antagonist PPADS against Signal Transducer and Activator of Transcription Proteins.Chembiochem : a European journal of chemical biology · 2025Article
- Ultrahigh-Throughput Virtual Screening Strategies against PPI Targets: A Case Study of STAT Inhibitors.Journal of chemical information and modeling · 2025Article
- Targeting SIX2 as a novel sensitization strategy of sorafenib treatment on advanced hepatocellular carcinoma through modulating METTL9-SLC7A11 axis.NPJ precision oncology · 2025Article
- Biaryl Phosphates and Phosphonates as Selective Inhibitors of the Transcription Factor STAT4.Angewandte Chemie (International ed. in English) · 2025Article
- Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.Circulation research · 2025Article
- Development of mirror-image monobodies targeting the oncogenic BCR::ABL1 kinase.Nature communications · 2024Article
- A toolbox for enzymatic modification of nucleic acids with photosensitizers for photodynamic therapy.RSC chemical biology · 2024Article
- Review
- Stafiba: A STAT5-Selective Small-Molecule Inhibitor.Chembiochem : a European journal of chemical biology · 2023Article
- A High-Throughput Fluorescence Polarization-Based Assay for the SH2 Domain of STAT4.Methods and protocols · 2022Article
- Asymmetrically Substituted m-Terphenyl Phosphates Inhibit the Transcription Factor STAT5a.Chembiochem : a European journal of chemical biology · 2022Article
- Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription.Frontiers in oncology · 2021Article
- Article
- Applications of the Pharmacophore Concept in Natural Product inspired Drug Design.Molecular informatics · 2020Review
- Selective Modulation of Dynamic Protein Complexes.Cell chemical biology · 2020Review
- The Selectivity of Fosfosal for STAT5b over STAT5a is Mediated by Arg566 in the Linker Domain.Chembiochem : a European journal of chemical biology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Src homology 2 (SH2) domains play a central role in signal transduction. Although many SH2 domains have been validated as drug targets, their structural similarity makes development of specific inhibitors difficult. The cancer-relevant transcription factors STAT5a and STAT5b are particularly challenging small-molecule targets because their SH2 domains are 93% identical on the amino acid level. Here we present the natural product-inspired development of the low-nanomolar inhibitor Stafib-1, as the first small molecule which inhibits the STAT5b SH2 domain (K(i)=44 nM) with more than 50-fold selectivity over STAT5a. The binding site of the core moiety of Stafib-1 was validated by functional analysis of point mutants. A prodrug of Stafib-1 was shown to inhibit STAT5b with high selectivity over STAT5a in tumor cells. Stafib-1 provides the first demonstration that naturally occurring SH2 domains with more than 90% sequence identity can be selectively targeted with small organic molecules.
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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.