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- | STF-083010 / Shanghai Jiao Tong University
Journal: The total xanthones extracted from Gentianella acuta alleviates HFpEF by activating the IRE1?/Xbp1s pathway. (Pubmed Central) - Jun 7, 2024
impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1?/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.
- | STF-083010 / Shanghai Jiao Tong University
Journal: Bax Inhibitor-1 preserves pancreatic ?-cell proteostasis by limiting proinsulin misfolding and programmed cell death. (Pubmed Central) - May 15, 2024
These results uncover a new protective role for BI-1 in pancreatic ?-cell physiology as a stress integrator to modulate the UPR triggered by accumulating unfolded proinsulin in the ER, as well as autophagy and programmed cell death, with consequences on ?-cell function and insulin secretion. In pancreatic ?-cells, BI-1-/- deficiency perturbs proteostasis with proinsulin misfolding, ER stress, terminal UPR with overwhelmed IRE1?/XBP1s/CHOP activation, inflammation, ?-cell programmed cell death, and diabetes.
- | STF-083010 / Shanghai Jiao Tong University
Journal, IO biomarker: Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways. (Pubmed Central) - Apr 7, 2024
In pancreatic ?-cells, BI-1-/- deficiency perturbs proteostasis with proinsulin misfolding, ER stress, terminal UPR with overwhelmed IRE1?/XBP1s/CHOP activation, inflammation, ?-cell programmed cell death, and diabetes. PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.
- | STF-083010 / Shanghai Jiao Tong University
Journal, IO biomarker: Emodin, an Emerging Mycotoxin, Induces Endoplasmic Reticulum Stress-Related Hepatotoxicity through IRE1?-XBP1 Axis in HepG2 Cells. (Pubmed Central) - Aug 1, 2023
inhibitor, STF-083010, was used...Furthermore, the apoptosis rate was increased in a dose-dependent manner with emodin treatment. Thus, emodin induced ER stress in HepG2 cells by activating the IRE1?-XBP1 axis and induced apoptosis, indicating that emodin can cause hepatotoxicity.
- | STF-083010 / Shanghai Jiao Tong University
Journal: DHA induces adipocyte lipolysis through endoplasmic reticulum stress and the cAMP/PKA signaling pathway in grass carp (Ctenopharyngodon idella). (Pubmed Central) - May 1, 2023
and X-box binding protein 1 potentially participate in DHA-induced lipolysis...The present study elucidated the molecular mechanism for DHA-induced lipolysis in grass carp adipocytes and emphasized the importance of ER stress and the cAMP/PKA pathway in DHA-induced lipolysis. These results deepen our understanding of ameliorating lipids deposition in freshwater fish by targeting DHA.
- | STF-083010 / Shanghai Jiao Tong University
Journal: Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis. (Pubmed Central) - Apr 28, 2023
signaling in ER stress. These findings demonstrated that OTUD3 played a critical role in dopaminergic neuron neurodegeneration, which provided new evidence for the multiple and tissue-dependent functions of OTUD3.
- | STF-083010 / Shanghai Jiao Tong University, thapsigargin / University of Nottingham, Pirbright Institute
Journal: TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1?/TRAF2/NF-?B signalling. (Pubmed Central) - Mar 24, 2023
activator thapsigargin (TG). These data suggest that TSG-6 administration can effectively suppress the proliferation of HSFs in part via the inhibition of IRE1?-mediated ER stress-induced inflammation (IRE1?/TRAF2/NF-?B signalling).
- | STF-083010 / Shanghai Jiao Tong University
Journal: XBP1s acts as a transcription factor of IRE1? and promotes proliferation of colon cancer cells. (Pubmed Central) - Mar 14, 2023
Our findings reveal a previously unknown mechanism of IRE1? expression by XBP1s and highlight the role of this regulation in proliferation of colon cancer cells, suggesting that IRE1?-targeting is a potential therapeutic strategy for colon cancer.
- | STF-083010 / Shanghai Jiao Tong University
Journal: Erbin protects against sepsis-associated encephalopathy by attenuating microglia pyroptosis via IRE1α/Xbp1s-Ca axis. (Pubmed Central) - Oct 6, 2022
expression by XBP1s and highlight the role of this regulation in proliferation of colon cancer cells, suggesting that IRE1?-targeting is a potential therapeutic strategy for colon cancer. In SAE, Erbin inhibits IRE1/Xbp1s pathway activity and reduces the ER Ca influx to the cytoplasm, reducing microglial pyroptosis.
- | JNK-IN-8 - Dana-Farber Cancer Institute, University of North Carolina / Chapel Hill, STF-083010 / Shanghai Jiao Tong University, Ninlaro (ixazomib) / Takeda
Journal: Targeting autophagy increases the efficacy of proteasome inhibitor treatment in multiple myeloma by induction of apoptosis and activation of JNK. (Pubmed Central) - Jul 8, 2022
In this study we showed that combined inhibition of autophagy and the proteasome synergistically induces cell death in multiple myeloma. Hence, we consider the implication of pharmaceutical inhibition of autophagy together with proteasome inhibition and UPR-directed therapy as promising novel in vitro treatment strategy against multiple myeloma.
- | STF-083010 / Shanghai Jiao Tong University
Preclinical, Journal: ER Stress is Involved in Mast Cells Degranulation via IRE1α/miR-125/Lyn Pathway in an Experimental Intracerebral Hemorrhage Mouse Model. (Pubmed Central) - May 26, 2022
STF083010, an inhibitor of IRE1α, was administered intranasally at 1 h after ICH induction...The downregulation of Lyn kinase, tryptase, IL-17A, TNF-α, and decreased mast cells number were reversed by antimiR-125. The present findings demonstrate that IRE1α inhibition attenuates mast cells degranulation and neuroinflammation, at least partially, through IRE1α/miR-125/Lyn signaling pathway after ICH.
- | STF-083010 / Shanghai Jiao Tong University
Journal: Genetic and pharmacological inhibition of XBP1 protects against APAP hepatotoxicity through the activation of autophagy. (Pubmed Central) - Apr 9, 2022
Acetaminophen (APAP) hepatotoxicity induces endoplasmic reticulum (ER) stress which triggers the unfolded protein response (UPR) in hepatocytes...Pharmacological inhibition of XBP1 using pre-treatment with STF-083010 [STF, 75 mg/kg] and autophagy induction with Rapamycin [RAPA, 8 mg/kg] or blockade with Chloroquine [CQ, 60 mg/kg] was also undertaken in vivo...Genetic and pharmacological inhibition of Xbp1 specifically in hepatocytes ameliorated APAP-induced liver injury by enhancing autophagy and decreasing CYP2E1 expression. These findings provide the basis for the therapeutic restoration of ER stress and/or induction of autophagy in patients with hyperacute liver injury.
- | STF-083010 / Shanghai Jiao Tong University, thapsigargin / University of Nottingham, Pirbright Institute
Journal: Endoplasmic reticulum stress induces mitochondrial dysfunction but not mitochondrial unfolded protein response in SH-SY5Y cells. (Pubmed Central) - Mar 26, 2022
Inhibition of IRE1α ribonuclease with STF-083010 did not protect the SH-SY5Y cells from ER stress-induced mitochondrial dysfunction. STF-083010 itself had significant impact on both mitochondrial respiration and generation of ΔΨm, which has mainly been associated with the uncoupling of respiratory chain from ATP synthesis.
- | sevoflurane / Generic mfg.
Preclinical, Journal: Sevoflurane post-conditioning alleviated hypoxic-ischemic brain injury in neonatal rats by inhibiting endoplasmic reticulum stress-mediated autophagy via IRE1 signalings. (Pubmed Central) - Feb 24, 2022
ER stress contributes to autophagy induced by HIBI. Furthermore, sevoflurane post-conditioning significantly protects against HIBI in neonatal rats by inhibiting ER stress-mediated autophagy via IRE1-JNK-beclin1 signaling cascade.
- STF-083010 / Shanghai Jiao Tong University, Vanflyta (quizartinib) / Daiichi Sankyo
The Unfolded Protein Response Mediates Resistance in AML and Its Therapeutic Targeting Enhances TKI Induced Cell Death in FLT3-ITD+ AML (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3864;
Targeting IRE1α in FLT3-ITD + cells effectively decreases clonogenic growth and induces apoptosis. Our data demonstrate that hypoxia-mediated resistance against AC220 can be overcome by simultaneous IRE1α inhibition.
- | STF-083010 / Shanghai Jiao Tong University, PF-573228 / Pfizer
Journal: Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue. (Pubmed Central) - Nov 4, 2021
After treatment with IRE1α inhibitor STF-083010, the results showed that the expression of adipocyte inflammation-related genes interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) significantly were decreased...At the same time, Col XV regulates the inflammation induced by ER stress in adipocytes by promoting IRE1α/XBP1 (X-Box binding protein 1) signaling. Our study provides new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM.
- | STF-083010 / Shanghai Jiao Tong University, thapsigargin / University of Nottingham, Pirbright Institute
Journal: Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling. (Pubmed Central) - Sep 24, 2021
In addition, STF-083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.
- | STF-083010 / Shanghai Jiao Tong University
Preclinical, Journal: Astaxanthin mediated regulation of VEGF through HIF1α and XBP1 signaling pathway: An insight from ARPE-19 cell and streptozotocin mediated diabetic rat model. (Pubmed Central) - Sep 15, 2021
Additionally, treatment with HIF1α siRNA and IRE1 inhibitor STF-083010 also inhibited the expression of VEGF induced by HG and CoCl conditions...In streptozotocin-induced diabetic rat model, astaxanthin reduced the expression of HIF1α, XBP1, and VEGF as well as protected the abnormalities in the retinal layers induced by diabetes condition. Thus, astaxanthin may be used as a potential nutraceutical to prevent or treat retinal dysfunction in diabetic patients.
- | STF-083010 / Shanghai Jiao Tong University, Motrem (nangibotide) / Inotrem
Preclinical, Journal: Activation of TREM-1 induces endoplasmic reticulum stress through IRE-1α/XBP-1s pathway in murine macrophages. (Pubmed Central) - Sep 4, 2021
Besides, we found that blockade of TREM-1 with LR12 ameliorated ER stress induced by LPS in vitro and in vivo. In conclusion, we conclude that TREM-1 activation induces ER stress through the IRE-1α/XBP-1s pathway in macrophages, contributing to the pro-inflammatory microenvironment.
- | STF-083010 / Shanghai Jiao Tong University, GSK2606414 / GSK, Institute of Cancer Research, Dartmouth College
Preclinical, Journal: Porcine epidemic diarrhea virus infections induce autophagy in Vero cells via ROS-dependent endoplasmic reticulum stress through PERK and IRE1 pathways. (Pubmed Central) - Aug 7, 2021
Furthermore, PEDV induced autophagy to promote viral replication via PERK and IER1 pathways in Vero cells. These results provide the mechanism of PEDV-induced ROS-dependent ER stress-mediated autophagy in Vero cells through activating PERK and IRE1 pathways.
- | STF-083010 / Shanghai Jiao Tong University
Journal: A Human IRE1 Inhibitor Blocks the Unfolded Protein Response in the Pathogenic Fungus Aspergillus fumigatus and Suggests Noncanonical Functions within the Pathway. (Pubmed Central) - Jul 22, 2021
However, these phenotypes were surprisingly narrow in scope relative to those associated with a complete deletion of the hacA gene. These findings expand the understanding of UPR signaling in this species by supporting the existence of noncanonical functions for the unspliced hacA mRNA in ER stress response.
- | STF-083010 / Shanghai Jiao Tong University
Journal: Dual role of inositol-requiring enzyme 1α (IRE-1α) in Cd-induced apoptosis in human renal tubular epithelial cells: endoplasmic reticulum stress and STAT3 signaling activation. (Pubmed Central) - Jun 23, 2021
Mechanistically, Cd promoted the binding of IRE-1α with signal transducer and activator of transcription-3 (STAT3) leading to elevated phosphorylation of STAT3 at Ser727 and thus inactivation of STAT3 signaling, which resulted in aggravation of Cd-induced apoptosis in HK-2 cells. Collectively, our findings indicate that IRE-1α coordinate ER stress and STAT3 signaling in mediating Cd-induced renal toxicity, suggesting that targeting IRE-1α might be a potential therapeutic approach for Cd-induced renal dysfunction and disease.
- | STF-083010 / Shanghai Jiao Tong University
Journal, IO biomarker: MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress. (Pubmed Central) - Jun 16, 2021
Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were evaluated using BrdU, MTT, Annexin V-FITC/PI staining, and caspase-12 and -3 activities assays...Our results indicated that the apoptotic pathway was induced possibly through activation of caspases -12 and -3 and elevation of the Bax/Bcl-2 ratio. Overall, the present paper adds new evidence to the possible treatment of miR-30c-2-3p via impeding the XBP1 transcription in ovarian cancer cells provoking apoptotic pathways by XBP1/CHOP/BIM mediators.
- Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] TARGETING THE IRE1Α-XBP1 PATHWAY INDUCES APOPTOSIS IN FLT3-ITD+ AML AND ENHANCES THE EFFECT OF TKI INDUCED FLT3-ITD INHIBITION () - May 13, 2021 - Abstract #EHA2021EHA_903;
Results Pharmacological inhibition of the IRE1α RNase activity using STF-083010 blocked XBP1 splicing and reduced the cell viability of human AML cell lines in a dose dependent way...Targeting IRE1α in FLT3-ITD+ cells is effective to decrease proliferation, clonogenic potential and induces apoptosis. Our data demonstrate that hypoxia-conferred resistance against AC220 can be overcome by simultaneous IRE1α inhibition, making this pathway an interesting novel therapeutic target.