ArticleJournal of medicinal chemistry2019
Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 205 citations in OpenAlex.
- Trial
- STAT3 signaling inhibitors for cancer treatment.Trends in pharmacological sciences · 2026Review
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Discovery of SD-2301 as a Highly Potent and Selective PROTAC STAT3 Degrader Capable of Achieving Complete Tumor Regression with Single Administration.Journal of medicinal chemistry · 2026Article
- Kinetic control of macrophage death by PTM-turnover crosstalk in infection and inflammation.Cell chemical biology · 2026Review
- Identification and Biological Evaluation of Juglone-Derived STAT3 Inhibitors against Colorectal Cancer.ACS medicinal chemistry letters · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Fusion Molecules Between the STAT5b Inhibitor Stafib-2-CR and a Cereblon Ligand.ChemistryOpen · 2026Article
- Discovery of SD-965 as a Potent, Selective, and Efficacious STAT3 PROTAC Degrader.Journal of medicinal chemistry · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities.Frontiers in immunology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- An Update on Clinically Advanced PROTAC Degraders and Their Synthesis.Molecules (Basel, Switzerland) · 2025Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation.Drug development research · 2025Review
- STAT3 expression in brain metastases from breast cancer is correlated with molecular subtype and impacts clinical outcome.Neuro-oncology · 2025Article
- Targeted NAT10 Degradation by PROTAC NP1192 Suppresses Hypoxia-Adaptive Glycolysis and Reinvigorates CD8ACS central science · 2025Article
- Biaryl Phosphate-Based Inhibitors of the Transcription Factor STAT4.ChemMedChem · 2025Article
- Proteolysis-targeting chimeras in cancer therapy: Targeted protein degradation for next-generation treatment.Cancer · 2025Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and an attractive therapeutic target for cancer and other human diseases. Despite 20 years of persistent research efforts, targeting STAT3 has been very challenging. We report herein the structure-based discovery of potent small-molecule STAT3 degraders based upon the proteolysis targeting chimera (PROTAC) concept. We first designed SI-109 as a potent, small-molecule inhibitor of the STAT3 SH2 domain. Employing ligands for cereblon/cullin 4A E3 ligase and SI-109, we obtained a series of potent PROTAC STAT3 degraders, exemplified by SD-36. SD-36 induces rapid STAT3 degradation at low nanomolar concentrations in cells and fails to degrade other STAT proteins. SD-36 achieves nanomolar cell growth inhibitory activity in leukemia and lymphoma cell lines with high levels of phosphorylated STAT3. A single dose of SD-36 results in complete STAT3 protein degradation in xenograft tumor tissue and normal mouse tissues. SD-36 achieves complete and long-lasting tumor regression in the Molm-16 xenograft tumor model at well-tolerated dose-schedules. SD-36 is a potent, selective, and efficacious STAT3 degrader.
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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.