^
2ms
Enhanced anti-tumor efficacy of S3I-201 in breast cancer mouse model through Wharton jelly- exosome. (PubMed, Cancer Cell Int)
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.
Preclinical • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CASP3 (Caspase 3)
|
GLG-302
3ms
Combining proteomics and Phosphoproteomics to investigate radiation-induced rectal fibrosis in rats and the effects of pSTAT3 inhibitor S3I-201 on human intestinal fibroblasts. (PubMed, J Proteomics)
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.
Preclinical • Journal
|
TGFB1 (Transforming Growth Factor Beta 1) • CTGF (Connective tissue growth factor)
|
GLG-302
4ms
Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia. (PubMed, Fitoterapia)
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.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
GLG-302
5ms
Methoxylated Flavones from Casimiroa edulis La Llave Suppress MMP9 Expression via Inhibition of the JAK/STAT3 Pathway and TNFα-Dependent Pathways. (PubMed, J Agric Food Chem)
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.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • MMP9 (Matrix metallopeptidase 9)
|
GLG-302
7ms
PLAU promotes cell proliferation and migration of head and neck cancer via STAT3 signaling pathway. (PubMed, Exp Cell Res)
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.
Journal
|
PLAU (Plasminogen Activator) • TNFRSF12A (TNF Receptor Superfamily Member 12A)
|
GLG-302
7ms
PDP1 promotes the progression of breast cancer through STAT3 pathway. (PubMed, Cell Biochem Funct)
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.
Journal
|
PDP1 (Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 1)
|
PD-1-L • STAT3 overexpression
|
GLG-302
10ms
Brain Metastases Are Regulated by Immuno-inflammatory Signaling Pathways Governed by STAT3, MAPK and Tumor Suppressor p53 Status: Possible Therapeutic Targets. (PubMed, Anticancer Res)
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.
Journal • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53)
|
PD-L1 expression • TP53 mutation • STAT3 mutation • TP53 expression
|
GLG-302
over1year
The protective effect of leukemia inhibitory factor on apoptosis of BMSCs induced by hypoxia and serum-deprivation. (PubMed, Am J Transl Res)
These data indicated that LIF played a protective role in apoptosis of BMSCs induced by ischemia via activating JAK1/STAT3 signaling pathway.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • JAK1 (Janus Kinase 1) • CASP3 (Caspase 3) • ANXA5 (Annexin A5)
|
GLG-302
over1year
Cold plasma and inhibition of STAT3 selectively target tumorigenicity in osteosarcoma. (PubMed, Redox Biol)
By proposing a combined treatment, our results demonstrate that the deleterious pro-stemness signals mediated by PTL can be abrogated when this is combined with the STAT3 inhibitor S3I-201, resulting in a strong suppression of in vivo tumor growth...We anticipate our work to be a starting point for wider studies using relevant 3D tumor models to evaluate the effects of plasma-based therapies on tumor subpopulations of different cancer types. Furthermore, combination with STAT3 inhibition or other suitable cancer type-specific targets can be relevant to consolidate the development of the field.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
GLG-302
almost2years
STAT3 promotes differentiation of monocytes to MDSCs via CD39/CD73-adenosine signal pathway in oral squamous cell carcinoma. (PubMed, Cancer Immunol Immunother)
Furthermore, we found that S3I-201 displayed prominent anti-tumor efficacy in C3H/He OSCC mouse model via inhibiting CD39/CD73-adenosine signal pathway and decreasing MDSCs. These results suggest that STAT3 signal can induce the differentiation of monocytes into MDSCs in tumor microenvironment depending on CD39/CD73-adenosine signal pathway and STAT3 blockade is a promising therapeutic strategy for OSCC.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3) • CD33 (CD33 Molecule) • NT5E (5'-Nucleotidase Ecto) • CD14 (CD14 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
|
GLG-302
2years
Design, synthesis, and biological characterization of a potent STAT3 degrader for the treatment of gastric cancer. (PubMed, Front Pharmacol)
We first synthesized an analog of the STAT3 inhibitor S3I-201 as a ligand, using the cereblon (CRBN)/cullin 4A E3 ligase ligand pomalidomide to synthesize a series of PROTACs. Among them, the SDL-1 achieves the degradation of STAT3 protein in vitro, and exhibits good anti-gastric cancer cell proliferation activity, inhibits invasion and metastasis of MKN1 cell, and induces MKN1 cell apoptosis and arrests cell cycle at the same time. Our study shows that SDL-1 is a potent STAT3 degrader and may serve as a potential anti-gastric cancer drug, providing ideas for further development of drugs for clinical use.
Journal
|
CRBN (Cereblon) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CUL4A (Cullin 4A)
|
pomalidomide • GLG-302
over2years
The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma. (PubMed, Aging (Albany NY))
The promotional effect upon downregulation of CFHR3 induced by CFHR3 stable knockdown or miR-590-3p on HCC cell malignant phenotypes is attenuated by STAT3 inhibitor, S3I-201. In conclusion, our results reveal that CFHR3 is a protective biomarker for HCC patients, and targeting the miR-590-3p/CFHR3/p-STAT3/p53 signaling axis provides a promising strategy for HCC therapeutics.
Journal
|
TP53 (Tumor protein P53)
|
TP53 expression
|
GLG-302
over2years
Pancreatic cancer growth promoted by bone marrow mesenchymal stromal cell-derived IL-6 is reversed predominantly by IL-6 blockade. (PubMed, Cytotherapy)
In addition, in a heterotopic nude mouse model of human pancreatic tumor xenografts, blockade of IL-6 with the anti-IL-6 receptor antibody, tocilizumab, or of its downstream effector STAT3 with the small molecule STAT3 inhibitor S3I-201, abrogated MSC-mediated tumor promotion and delayed tumor formation significantly. Our data demonstrate that MSCs promote pancreatic cancer growth, with IL-6 produced by MSCs playing a pivotal role.
Journal
|
CXCL8 (Chemokine (C-X-C motif) ligand 8)
|
IL6 expression
|
Actemra IV (tocilizumab) • GLG-302
over2years
Hepatocyte growth factor protects pulmonary endothelial barrier against oxidative stress and mitochondria-dependent apoptosis. (PubMed, Chin Med J (Engl))
In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • HGF (Hepatocyte growth factor) • CDH5 (Cadherin 5)
|
GLG-302
over2years
Suppression of the Proliferation of Huh7 Hepatoma Cells Involving the Downregulation of Mutant p53 Protein and Inactivation of the STAT 3 Pathway with Ailanthoidol. (PubMed, Int J Mol Sci)
Consistent with ATD, the administration of S3I201 (STAT 3 inhibitor) reduced the expression of Bcl-2/Bcl-xL, cyclin D1, mutp53, and MVK. These results demonstrated ATD's selectivity against mutp53 hepatoma cells involving the downregulation of mutp53 and inactivation of STAT3.
Journal • PARP Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • BCL2L1 (BCL2-like 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CDK2 (Cyclin-dependent kinase 2) • TGFB1 (Transforming Growth Factor Beta 1) • ANXA5 (Annexin A5)
|
TP53 mutation • TP53 wild-type • BCL2 expression • CCND1 expression • TP53 expression • STAT3 expression • BAX expression • TP53 Y220C • CDK2 expression
|
GLG-302
over2years
Serine 727 phosphorylation is necessary to induce the STAT3-mediated transcription of LINC00184 in oesophageal squamous cell carcinoma. (PubMed, Mol Cell Biochem)
The dephosphorylation of STAT3 with NSC74859 was shown to be unable to suppress the expression of LINC00184 in vivo in a xenograft mouse model. Moreover, STAT3, once phosphorylated at serine 727, tended to translocate into the mitochondria to promote LINC00184 expression in ESCC cells. Together, these data strongly support the oncogenic role of LINC00184 in ESCC.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
GLG-302
over2years
Anlotinib combined with temozolomide suppresses glioblastoma growth via mediation of JAK2/STAT3 signaling pathway. (PubMed, Cancer Chemother Pharmacol)
Anlotinib exerts anti-glioblastoma activity possibly through the JAK2/STAT3/VEGFA signaling pathway. TMZ potentiated the anti-glioblastoma effect of anlotinib via the same signaling pathway, indicating the potential application of anlotinib as a treatment option for glioblastoma.
Journal
|
BECN1 (Beclin 1)
|
Focus V (anlotinib) • temozolomide • GLG-302
3years
Anti-Gastric Cancer Effect of Purified Omphalia lapidescens Protein via Regulating the JAK/STAT3 Signaling Pathway. (PubMed, Nutr Cancer)
Interleukin-6 (IL-6) and NSC74859 were used as the agonist and inhibitor of the JAK/STAT3 signaling pathway, respectively...The expression of the crucial members in the pathway of MC-4 cells, including glycoprotein 130 (GP130), JAK1, JAK2, STAT3, p-STAT3, suppressor of cytokine signaling SOCS1 and SOCS3, was detected by western blotting. pPeOp exhibited promising anticancer effect in the xenograft nude mice model, established by STAT3 knock down gastric cancer cells.Thus, JAK/STAT3 inhibition partially contributed to the anticancer effect of pPeOp, which may serve as a novel strategy for gastric cancer.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1960385.
Journal
|
JAK2 (Janus kinase 2) • IL6 (Interleukin 6) • JAK1 (Janus Kinase 1) • SOCS1 (Suppressor Of Cytokine Signaling 1)
|
GLG-302
over3years
Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway. (PubMed, J Inflamm Res)
Similarly, plasma IL-6 levels in ALL, ALL-tocilizumab (TCZ, an IL-6 receptor inhibitor) and ALL-S3I-201 (a selective inhibitor of STAT3) mice were increased compared to the control group. These effects were attenuated by blocking IL-6/STAT3/PXR signaling pathway. Inflammation-mediated changes in pharmacokinetics are thought to be executed through pathways IL-6-activated pathways, which can facilitate a better understanding of the potential for the use of IL-6 to predict the severity of adverse outcomes and the major implications on potential ALL treatments.
Journal
|
IL6 (Interleukin 6)
|
IL6 expression
|
Actemra IV (tocilizumab) • GLG-302
over3years
Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin. (PubMed, Bioengineered)
Dual luciferase reporter assay showed that FTO promoter activity was inhibited by S3I-201 (STAT3 inhibitor) but enhanced by epidermal growth factor (EGF, STAT3 activator) in BC-DoxR and BC cells. Moreover, decreased doxorubicin resistance by STAT3 knockdown was abolished by FTO overexpression and decreased doxorubicin sensitivity by STAT3 overexpression was reversed by FTO knockdown, indicating that FTO was implicated in STAT3-mediated doxorubicin resistance and impairment of doxorubicin sensitivity of BC cells. Altogether, our findings provide a mechanism underlying BC doxorubicin resistance.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3) • EGF (Epidermal growth factor) • FTO (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
|
STAT3 expression • FTO expression • FTO overexpression
|
doxorubicin hydrochloride • GLG-302
over3years
Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells. (PubMed, Mol Oncol)
The CTRP8-RXFP1 ligand-receptor system protects human GBM cells against the DNA alkylating damage inducing temozolomide (TMZ), the drug of choice for the treatment of patients with GBM. This coincided with enhanced activity of ezrin, a key factor in tethering F-actin to the plasma membrane, and inhibition of the actin filament severing activity of cofilin. The Cdc42 mediated F-actin remodeling and pro-migratory action of the novel RXFP1-JAK3-STAT3-Cdc42 axis was blocked by JAK3 inhibitor Tofacitinib and STAT3 inhibitor S3I-201 and provides a new rationale for the design of JAK3 and STAT3 inhibitors with better brain permeability for clinical treatment of the pervasive brain invasiveness of GBM.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • JAK3 (Janus Kinase 3)
|
temozolomide • tofacitinib • GLG-302
almost4years
Leukemia inhibitory factor protects photoreceptor cone cells against oxidative damage through activating JAK/STAT3 signaling. (PubMed, Ann Transl Med)
LIF was observed to block these events; however, the administration of the STAT3 inhibitor S3I201 reversed the beneficial effects of LIF on HO-triggered apoptosis and ROS production. In conclusion, the present study suggested that LIF may relieve oxidative damage in cone cells through suppressing apoptosis and oxidative stress by targeting the STAT3 signaling pathway.
Journal • IO biomarker
|
BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
|
BCL2 expression • BAX expression
|
GLG-302
almost4years
Chemerin reverses the malignant phenotype and induces differentiation of human hepatoma SMMC7721 cells. (PubMed, Arch Pharm Res)
Chemerin decreased phosphorylated ERK and AKT expression and the cell proliferation induced by PI3K activator 740 Y-P but could not significantly alter phosphorylated STAT3 expression and the cell growth induced by STAT3 inhibitor NSC74859. In conclusion, chemerin reversed the malignant phenotype and induced SMMC7721 cell differentiation by inhibiting MAPK/ERK and PI3K/AKT signaling; growth inhibition by chemerin is not directly related to the JAK/STAT signaling pathway. Our study provides novel evidence that chemerin could be utilized for liver cancer treatment.
Journal
|
TERT (Telomerase Reverse Transcriptase) • AFP (Alpha-fetoprotein) • IGF2 (Insulin-like growth factor 2) • VIM (Vimentin) • ALB (Albumin)
|
VIM expression
|
GLG-302
almost4years
Down-regulation of Autophagy-Associated Protein Increased Acquired Radio-Resistance Bladder Cancer Cells Sensitivity to Taxol. (PubMed, Int J Radiat Biol)
Long-term FI treatment is an effective method to establish the ARR-phenotype BCa cell model, by enriching BCSCs and enhancing cells migration and invasion. Both inhibiting the expression of autophagy-related proteins and using autophagy inhibitor can increase the sensitivity of ARR cells to taxol, suggesting that autophagy may play an important role in ARR cells chemical tolerance.
Journal
|
MMP9 (Matrix metallopeptidase 9) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
paclitaxel • GLG-302 • chloroquine phosphate
almost4years
Inflammatory microenvironment of fibrotic liver promotes hepatocellular carcinoma growth, metastasis and sorafenib resistance through STAT3 activation. (PubMed, J Cell Mol Med)
In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti-apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I-201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up-regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • STAT3 (Signal Transducer And Activator Of Transcription 3)
|
sorafenib • GLG-302
almost4years
Eucannabinolide, a novel sesquiterpene lactone, suppresses the growth, metastasis and BCSCS-like traits of TNBC via inactivation of STAT3. (PubMed, Neoplasia)
Moreover, introduction of STAT3-short hairpin RNAs or STAT3 inhibitor S3I-201 attenuates the Euc-induced inhibition of cell viability...In conclusion, Euc elicits the effects of anti-proliferation, anti-metastasis and anti-breast cancer stem cell-like traits in TNBC via targeting STAT3. These data highlight that development of Euc as a STAT3 inhibitor may offer a promising therapeutic strategy for TNBC.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
GLG-302
4years
[VIRTUAL] Biological and Clinical Impact of JAK2/mTOR Blockade in Gvhd Prevention: Preclinical and Phase I Trial Results (ASH 2020)
In this first-in-human phase I/II GVHD prevention trial we combine pacritinib, a JAK2 inhibitor, with sirolimus to concurrently reduce T-cell costimulation via mTOR and IL-6 activity...To test the efficacy of dual JAK2/mTOR inhibition in vivo, NSG mice were transplanted with human peripheral blood mononuclear cells (PBMCs) and treated with either vehicle, PAC, STAT3 inhibitor S3I-201, SIR, PAC/SIR, or S3I/SIR... We demonstrate that PAC/SIR/TAC (RP2D: PAC 100mg twice a day) is safe and effectively reduces IL-6 signal transduction, pathogenic Th1 and Th17 cells, and preserves Tregs and effectors necessary for GVL and antiviral immunity. Preliminarily, adding pacritinib limits acute GVHD, preserves donor CMV immunity, and permits timely engraftment. The efficacy of PAC/SIR/TAC will be tested in our ongoing phase II GVHD prevention trial.
P1 data
|
JAK2 (Janus kinase 2) • CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • JAK3 (Janus Kinase 3)
|
sirolimus • Vonjo (pacritinib) • GLG-302
4years
EFTUD2 maintains the survival of tumor cells and promotes hepatocellular carcinoma progression via the activation of STAT3. (PubMed, Cell Death Dis)
Further verification indicated that EFTUD2-overexpressing cells exhibited an EMT-like phenotype and had enhanced STAT3 activation, while the STAT3 inhibitor S3I-201 partially blocked these pro-malignant effects of EFTUD2 overexpression. In summary, we report EFTUD2 as a novel oncogene that helps to maintain the survival of HCC cells and promotes HCC progression through the activation of STAT3. The high level of expression of EFTUD2 in HCC tissues indicates shorter overall and recurrence-free survival in HCC patients.
Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3)
|
GLG-302
4years
Thermal Ablation Induces Transitory Metastatic Growth by Means of the STAT3/c-Met Molecular Pathway in an Intrahepatic Colorectal Cancer Mouse Model. (PubMed, Radiology)
Finally, PHA-665752 and S3I-201 were used to block c-Met or STAT3, respectively, prior to either RFA or sham treatment (six animals per arm, n = 96).
Preclinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • IL6 (Interleukin 6) • HGF (Hepatocyte growth factor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD34 (CD34 molecule)
|
GLG-302 • PHA665752
over4years
STAT3-PTTG11 abrogation inhibits proliferation and induces apoptosis in malignant glioma cells. (PubMed, Oncol Lett)
PTTG11 suppression via siRNA inhibited the viability and increased the apoptosis of glioma cells induced by the STAT3 activator S3I-201. c-Myc and Bcl-2 expression was suppressed by PTTG11 inhibition. The findings of the present study suggest that the STAT3-PTTG11 signaling pathway may play an important role in glioma progression by regulating cell proliferation and apoptosis.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • STAT3 (Signal Transducer And Activator Of Transcription 3)
|
BCL2 expression • MYC expression • BAX expression
|
GLG-302
over4years
Long non-coding RNA THOR promotes ovarian Cancer cells progression via IL-6/STAT3 pathway. (PubMed, J Ovarian Res)
Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.
Journal
|
IL6 (Interleukin 6)
|
Actemra IV (tocilizumab) • GLG-302
over4years
Exosomes derived from endoplasmic reticulum-stressed liver cancer cells enhance the expression of cytokines in macrophages via the STAT3 signaling pathway. (PubMed, Oncol Lett)
Furthermore, incubation of cells with ER stress-associated exosomes resulted inactivation of the Janus kinase 2/STAT3 pathway, and inhibition of STAT3 using S3I-201 in RAW264.7 cells significantly reduced cytokine production. Collectively, the present study identified a novel function of ER stress-associated exosomes in mediating macrophage cytokine secretion in the liver cancer microenvironment, and also indicated the potential of treating liver cancer via an ER stress-exosomal-STAT3 pathway.
Journal
|
JAK2 (Janus kinase 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • CCL2 (Chemokine (C-C motif) ligand 2)
|
GLG-302
over4years
The role of STAT3/mTOR-regulated autophagy in angiotensin II-induced senescence of human glomerular mesangial cells. (PubMed, Cell Signal)
Inhibition of oxidative stress with N-acetylcysteine (NAC) or interference with STAT3/mechanistic target of rapamycin (mTOR) activity with S3I-201 or STAT3-siRNA suppressed autophagy to a certain extent, which was conducive to delaying the senescence of glomerular mesangial cells. The antioxidant probucol reduced autophagy in human glomerular mesangial cells and alleviated the aging process of these cells by regulating STAT3/mTOR. These findings identify a role of STAT3/mTOR-regulated autophagy in Ang II-induced senescence of human glomerular mesangial cells and may provide a theoretical basis for anti-senescence treatment in clinical practice.
Journal
|
JAK2 (Janus kinase 2)
|
sirolimus • GLG-302
over4years
GABA, γ-Aminobutyric Acid, Protects Against Severe Liver Injury. (PubMed, J Surg Res)
Our results showed that preemptive treatment with GABA protected against severe acute liver injury in mice via GABA-mediated STAT3 signaling. Preemptive administration of GABA may be a useful approach to optimize marginal donor livers before transplantation.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • JAK2 (Janus kinase 2) • CASP3 (Caspase 3)
|
GLG-302
almost5years
Human pSTAT3-Inhibited Itregs Prevent Gvhd, Maintain Anti-Leukemia Immunity, and Increase Their Potency after Metabolic Reprogramming (TCT-ASTCT-CIBMTR 2020)
In human induced Tregs (iTregs), we demonstrated that inhibiting STAT3 phosphorylation (pSTAT3) with S3I-201 increases demethylated Foxp3 and significantly improves their suppressive potency in vitro, mitigating phenotypically plastic iTreg de-differentiation... We demonstrate that human pSTAT3-inhibited iTregs can prevent GVHD-mediated tissue damage, preserve anti-leukemia CTL function, and that metabolic reprogramming with coQ10 significantly enhances their suppressive potency. Based upon these data, we will clinically test the safety and efficacy of human pSTAT3-inhibited iTregs in GVHD prevention.
PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • FOXP3 (Forkhead Box P3)
|
GLG-302