Aug 8, 2021 · STAT3 oncogenic signaling has been implicated in immune regulatory mechanisms of multiple tumors [ 13 ]. For example, several studies showed that persistent activa-tion of STAT3 leads to the suppression of anti-tumor immunity by promoting Treg recruitment within the tumor microenvironment, while negatively regulating antitu-

Jul 8, 2021 · This Review aims to systematically summarize the progress of the last 5 years in the discovery of directive STAT3 small-molecule inhibitors and degraders, focusing primarily on their structural features, design strategies, and bioactivities.

Jan 8, 2021 · Direct STAT3 inhibitors comprise several groups based on the binding domain with STAT3. Current research on direct STAT3 inhibitors is focused on antagonizing the SH2, given its...

Sep 24, 2020 · Combination therapies of STAT3 inhibitors with currently therapeutic anti-tumor drugs including the immune-checkpoint inhibitors may open up new possibilities for long-lasting and multilayered tumor control.

Jun 25, 2021 · Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates various biological processes, including proliferation, metastasis, angiogenesis, immune response, and chemoresistance.

Sep 11, 2024 · Some STAT3 inhibitors, such as napabucasin, C188-9, and YY201, have achieved efficacy in a variety of human cancers by directly targeting STAT3 and inhibiting STAT3 activation, effectively suppressing tumorigenesis and …

Jul 5, 2020 · Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated downstream of a broad range of receptors particularly interleukin-6 (IL-6) family.

Jan 20, 2024 · Exosome-based inhibitors open up new horizons for STAT3 drug discovery. Chuang and co-workers found a novel STAT3 inhibitor, pacritinib, which overcomes temozolomide resistance via downregulating miR-21-enriched exosomes from M2 glioblastoma-associated macrophages [ 180 ].

Aug 22, 2022 · Small-molecule inhibitors of STAT3 like BP-1-102 and BTP analogues displayed great potential against various cancers, while natural products, as well as peptide and peptidomimetics, also showed promising application.

Oct 9, 2016 · Direct STAT3 inhibitors include the STAT3-decoys and the STAT3-antisense oligonucleotide based inhibitor ISIS-STAT3Rx (AZD9150) . The third group of compounds includes two re-purposed drugs that also inhibit STAT3—the antiparasitic drug pyrimethamine and the HMG-CoA inhibitor Simvastatin [294–296].

Jul 15, 2021 · Inhibitors targeting STAT3 mRNA: Antisense oligonucleotides (ASOs) can inhibit STAT3 expression and function by downregulating STAT3 messenger RNA (mRNA) [53,54]. For example, danvatirsen, also known as AZD9150 or ISIS 481464, has been shown to reduce STAT3 mRNA and protein levels and block cell proliferation.

Oct 1, 2019 · In this review, we discuss recent scientific findings that provide insight into the variable therapeutic effects of targeting STAT3 therapy, review recent advances in diverse mechanisms of oncogenic STAT3 activation and focus on STAT3 inhibitors from clinical drugs and natural products.

In silico computational modeling, drug affinity responsive target stability (DARTS), and fluorescence polarization (FP) assays altogether determined that 323–1 and 323–2 directly target the STAT3 SH2 domain and inhibited both phosphorylated …

Jan 1, 2021 · In this review we discuss the importance of STAT3-dependent functions in cancer, review the status of compounds designed as direct-acting STAT3 inhibitors, and describe some of the strategies for repurposing of drugs as STAT3 inhibitors for cancer therapy.

In this paper, we reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation …

Nov 1, 2023 · Introduction: Signal transducer and activator of transcription 3 (STAT3) is ubiquitously hyper-activated in numerous cancers, rendering it an appealing target for therapeutic intervention.

Herein, we have found that at least 24 different anti-neoplastic agents—standard toxic chemotherapeutic agents, targeted kinase inhibitors, anti-hormonal agents, and monoclonal antibodies—that utilize the STAT3 signaling pathway as one mechanism of developing therapeutic resistance.

Aug 7, 2024 · To date, a variety of STAT3 inhibitors have been disclosed, such as peptides, peptidomimetics, and oligonucleotides, which can effectively block the dimerization and nuclear translocation of STAT3.

Because of the important role of STAT3, a large number of studies have been obtained. At the same time, after more than 20 years of development, STAT3 has also been used as a target for drug therapy. And the discovery of small molecule inhibitors also promoted the study of STAT3.

PIAS and the JAK-STAT pathway.Upon stimulation by IL-6, PIAS3 can inhibit transcription activation by activated STAT3.. Protein inhibitor of activated STAT (PIAS), also known as E3 SUMO-protein ligase PIAS, is a protein that regulates transcription in mammals.PIAS proteins act as transcriptional co-regulators with at least 60 different proteins in order to either activate or repress transcription.