GLG-302

This study reveals the critical role of FUBP3 in lung cancer metastasis and identifies a new regulatory axis involving FUBP3-STAT3-Twist1. FUBP3 interacts with STAT3, enhancing STAT3-dependent Twist1 expression, which promotes EMT and metastasis. FUBP3 functions as a prognostic biomarker, and STAT3 inhibitors present therapeutic strategies for lung cancer, offering novel insights for precision treatment.

Critically, the STAT3 inhibitor S3I-201 abrogated the pro-tumorigenic effects of BMX overexpression on HT29 cell proliferation, migration, and invasion. In conclusion, our findings establish that BMX drives CRC progression by activating STAT3 signaling pathway, which subsequently suppresses E-cadherin expression to induce EMT.

JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; Epub ahead of print.

We systematically discuss therapeutic strategies, including JAK inhibitors (tofacitinib, ruxolitinib), Src Homology 2 domain inhibitors (S3I-201, STATTIC), antisense oligonucleotides (AZD9150), and nanomedicine-based drug delivery systems, which enhance specificity and bioavailability while reducing toxicity. By integrating molecular mechanisms, disease pathology, and emerging therapeutic interventions, this review fills a critical knowledge gap in STAT3-targeted therapy. Our insights into STAT3 signaling crosstalk, epigenetic regulation, and resistance mechanisms offer a foundation for developing next-generation STAT3 inhibitors with greater clinical efficacy and translational potential.

Our results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.

In our research, we utilized TMT labeling alongside LC-MS/MS techniques for an in-depth exploration of both proteomic and phosphoproteomic landscapes in rat models of radiation-induced intestinal fibrosis (RIRF). Our analysis shed light on the function and pathways of proteins and phosphorylated proteins triggered by radiation, as well as those offering protection against it. We mapped out a network of interactions within these proteins and validated the expression levels of key proteins through quantitative measures. Additionally, the study ventured into identifying STAT3 as a potential therapeutic target, evaluating the efficacy of the S3I-201 inhibitor in laboratory settings, and suggesting its utility for RIRF treatment. Overall, our findings provide groundbreaking insights into RIRF's underlying mechanisms, laying a solid foundation for developing future antifibrotic treatments.

Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 μM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

In addition, AG490 and S3I-201, inhibitors of Janus kinase (JAK) and STAT3, suppressed LPS-mediated MMP9 induction, suggesting that the casedulones suppressed MMP9 induction through the inhibition of JAK/STAT3 pathways...Moreover, tumor necrosis factor-α (TNFα)-mediated MMP9 induction was significantly suppressed in the presence of the casedulones. Taken together, these findings suggest that casedulones inhibit the IL-6/STAT3 and TNFα pathways, which all involve LPS-mediated MMP9 induction.

A recovery assay using S3I-201, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), indicated that PLAU promoted HNC cell line progression via STAT3 signaling in vitro...In summary, we identified the tumorigenic PLAU function in the HNC progress. PLAU may represent a potential prognostic biomarker of HNC and the PLAU-STAT3 pathway might be considered a therapeutic target of HNC.

Cell counting kit-8 assay showed that PDP1 overexpression significantly raised MDA-MB-231 and MCF7 cell viability while STAT3 inhibitor S3I-201 recovered the cell growth to normal level. To summarize, PDP1 promotes the progression of BC through STAT3 pathway by regulating p-STAT3. The findings contribute to understanding the molecular mechanisms underlying BC progression, and opening avenues for targeted therapeutic approaches.

Activation of STAT3 and ERK1/2 promotes BM and provides compelling evidence for use of STAT3, ERK1/2 and p53 status as potential immunotherapeutic targets in BM.

These data indicated that LIF played a protective role in apoptosis of BMSCs induced by ischemia via activating JAK1/STAT3 signaling pathway.