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18d
Melatonin Promotes Neurogenesis via the JAK2/STAT3 Pathway in Hypoxic-Ischemic Neonatal Rats. (PubMed, Neurochem Res)
In addition, the use of a JAK2 inhibitor (WP1066) and agonist (C-A1) verified that Mel exerted its protective effects by down-regulating the JAK2/STAT3 pathway. Morris water maze further confirmed that Mel improved spatial learning and memory function in neonatal rats with HIBD. Multimodal MRI offers a visual basis for monitoring metabolic changes and therapeutic effects, while Mel enhances neurogenesis and mitigates brain injury through inhibition of the JAK2/STAT3 pathway, thus providing a theoretical basis for the clinical application of Mel in HIBD in neonates.
Preclinical • Journal
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NES (Nestin)
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WP1066
1m
WP1066 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
P2, N=39, Recruiting, Northwestern University | Active, not recruiting --> Recruiting
Enrollment open
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
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RAS wild-type • IDH wild-type
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WP1066
2ms
First-in-child phase I trial of p-STAT3 inhibitor WP1066 in pediatric brain tumor patients. (PubMed, JCI Insight)
WP1066 is safe, has minimal toxicity, and induces anti-tumor immune responses in pediatric brain tumor patients. Phase II investigation of WP1066 at the MFD in this patient population is warranted.
P1 data • Journal
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CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD4 (CD4 Molecule)
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WP1066
3ms
Allicin reduces airway inflammation and remodeling in a murine asthmatic model. (PubMed, Biochem Biophys Res Commun)
The STAT3 agonist Colivelin reverses the anti-proliferative effects of allicin, while the inhibitor WP1066 enhances these effects. These findings collectively suggest that allicin exerts its anti-inflammatory and anti-remodeling effects in asthma by targeting the STAT3/PIM1 pathway, providing a new therapeutic strategy for asthma treatment.
Preclinical • Journal
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PIM1 (Pim-1 Proto-Oncogene) • TGFB1 (Transforming Growth Factor Beta 1) • IL13 (Interleukin 13) • IL4 (Interleukin 4) • IL5 (Interleukin 5)
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WP1066
3ms
SPP1+ macrophages promote colorectal cancer progression by activating JAK2/STAT3 signaling pathway. (PubMed, Sci Rep)
In contrast, after the cells were co-treated with WP1066 on the basis of co-culture with SPP1+ TAMs, MC38 cell viability was decreased, and apoptosis was increased; the levels of JAK2, STAT3, and their phosphorylation were decreased, and the EMT process was inhibited. Therefore, SPP1+ TAMs promote CRC cell proliferation and EMT by activating JAK2/STAT3 signaling pathway.
Journal
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SPP1 (Secreted Phosphoprotein 1) • CXCL9 (Chemokine (C-X-C motif) ligand 9)
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WP1066
6ms
WP1066 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
P2, N=39, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting
Enrollment closed
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
RAS wild-type • IDH wild-type
|
WP1066
7ms
Characterization of radiation electrophysiological properties of U87 cells induced by ionizing radiation and STAT3 inhibitors under microelectrode matrix sensor. (PubMed, Brain Res Bull)
This novel study establishes a practical and theoretical foundation for radiation electrophysiology research by demonstrating that the cellular impedance-sensing system based on microelectrode arrays can detect ionizing radiation-induced and drug-induced glioblastoma cell death in real-time.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • CASP3 (Caspase 3)
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WP1066
8ms
STAT3 inhibition in combination with CD47 blockade inhibits osteosarcoma lung metastasis. (PubMed, Front Immunol)
Here we investigated the therapeutic activity of the orally bioavailable STAT3 inhibitor, WP1066, and anti-CD47 antibody using OS mouse models...This was associated with increased frequency of activated CD8+ T cells, NK cells and macrophages in the lungs and LDLNs. Our preclinical studies support further investigation of targeting STAT3 and CD47 as novel immunotherapeutic approach against OS lung metastasis.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD80 (CD80 Molecule)
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WP1066
8ms
Role of the CEACAM7-JAK2/STAT3-BST2 Axis in the migration of nasopharyngeal carcinoma cells. (PubMed, Biochim Biophys Acta Mol Basis Dis)
These findings indicate that the CEACAM7/JAK2/STAT3/BST2 axis plays a crucial role in promoting NPC cell migration and underscore its potential as a therapeutic target for mitigating NPC metastasis.
Journal
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JAK2 (Janus kinase 2) • CEACAM5 (CEA Cell Adhesion Molecule 5) • STAT3 (Signal Transducer And Activator Of Transcription 3)
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WP1066
9ms
PSME2 promotes malignant progression through autophagy modulation via IL-6/STAT3 signaling pathway in esophageal squamous cell carcinoma. (PubMed, Life Sci)
The study shows the promising role of PSME2 as a therapeutic target in ESCC management. The combined inhibition of PSME2 and activated pathways ensures effective suppression of tumor growth and proliferation, thus offering a novel strategy for better treatment outcomes in ESCC patients.
Journal
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IL6 (Interleukin 6)
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carfilzomib • WP1066 • chloroquine phosphate
9ms
A pH-Sensitive Nanosized Covalent-Organic Polymer for Enhanced Tumor Photodynamic Immunotherapy by Hypoxia Relief and STAT3 Inhibition. (PubMed, Adv Sci (Weinh))
The signal transducer and activator of transcription 3 (STAT3) inhibitor WP1066 is further encapsulated into COPs to form a WP1066-loaded COP (TVW)...The antitumor capacity of photodynamic immunotherapy is extensively investigated in a murine subcutaneous hepatocellular carcinoma model. This photo-immunotherapy may provide an effective combination regimen for the efficient treatment of solid tumors such as hepatocellular carcinoma.
Journal • PD(L)-1 Biomarker • IO biomarker
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STAT3 (Signal Transducer And Activator Of Transcription 3)
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PD-L1 expression
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WP1066
10ms
Molecular mechanisms underlying TXNIP's anti-tumor role in breast cancer, including interaction with a novel, pro-tumor partner: CAST. (PubMed, Cell Death Dis)
Finally, cells with high levels of TXNIP expression displayed increased susceptibility to IL-24 and WP1066, a specific STAT3 inhibitor, suggesting possible predictive value for TXNIP. Collectively, these findings unveil novel TXNIP-dependent pathways that may contribute to breast cancer pathogenesis, enriching our understanding of this molecule's intricate role in cancer and potentially paving the way for clinical translation.
Journal
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TXNIP (Thioredoxin Interacting Protein) • CAST (Calpastatin)
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WP1066