ArticleMolecular oncology2015
Hitting the right spot: Mechanism of action of OPB-31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3).
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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.
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Who cites it
52 citing papers in PubMed, 91 citations in OpenAlex.
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Out of Nucleus: Serine 727 Phosphorylation Orchestrates Non-Canonical STAT3 Functions-Relevance to Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Deciphering the metabolic landscape of colorectal cancer through the lens of AhR-mediated intestinal inflammation.Discover oncology · 2025Review
- Review
- Breaking the cancer code: a novel DNA minicircle to disable STAT3 in ovarian cancer cells SKOV3.Frontiers in pharmacology · 2025Article
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.Cell death and differentiation · 2024Article
- Human intraparietal sulcal morphology relates to individual differences in language and memory performance.Communications biology · 2024Article
- Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review).International journal of oncology · 2024Review
- An Isoxazoloquinone Derivative Inhibits Tumor Growth by Targeting STAT3 and Triggering Its Ubiquitin-Dependent Degradation.Cancers · 2023Article
- Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay.Journal of translational medicine · 2023Article
- Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway.International journal of oncology · 2022Article
- Article
- Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway.International journal of molecular sciences · 2021Article
- Review
- Review
- Targeting STAT3 with Proteolysis Targeting Chimeras and Next-Generation Antisense Oligonucleotides.Molecular cancer therapeutics · 2021Review
- Article
- The Role of Janus Kinase/STAT3 Pathway in Hematologic Malignancies With an Emphasis on Epigenetics.Frontiers in genetics · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB-31121, an anticancer compound currently in clinical trials, has been reported to affect STAT3 signaling, although its mechanism of action has not been unequivocally demonstrated. In this study, we used a combined computational and experimental approach to investigate the molecular target and the mode of interaction of OPB-31121 with STAT3. In parallel, similar studies were performed with known STAT3 inhibitors (STAT3i) to validate our approach. Computational docking and molecular dynamics simulation (MDS) showed that OPB-31121 interacted with high affinity with the SH2 domain of STAT3. Interestingly, there was no overlap of the OPB-31121 binding site with those of the other STAT3i. Computational predictions were confirmed by in vitro binding assays and competition experiments along with site-directed mutagenesis of critical residues in the STAT3 SH2 domain. Isothermal titration calorimetry experiments demonstrated the remarkably high affinity of OPB-31121 for STAT3 with Kd (10 nM) 2-3 orders lower than other STAT3i. Notably, a similar ranking of the potency of the compounds was observed in terms of inhibition of STAT3 phosphorylation, cancer cell proliferation and clonogenicity. These results suggest that the high affinity and efficacy of OPB-31121 might be related to the unique features and mode of interaction of OPB-31121 with STAT3. These unique characteristics make OPB-31121 a promising candidate for further development and an interesting lead for designing new, more effective STAT3i.
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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.