ArticleNature chemical biology2020
Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 180 citations in OpenAlex.
- IRE1α Is Associated with Host Lipid Biosynthesis During Human Coronavirus OC43 Infection.Viruses · 2026Article
- An ER stress-responsive RNA rheostat for programmable gene and mRNA therapies.Cell chemical biology · 2026Article
- Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life.The EMBO journal · 2026Article
- Multifunctional nanotherapeutics for targeted modulation of endoplasmic reticulum stress to potentiate cancer therapy.Asian journal of pharmaceutical sciences · 2026Review
- Single-Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chemical modulation of the unfolded protein response reveals an antiviral role for the PERK pathway in human coronavirus 229E infection.RSC chemical biology · 2026Article
- Inhibition of N-Terminal Acetyltransferase C Mitigates Endoplasmic Reticulum Stress-Mediated Muscle Atrophy in Cancer Cachexia.Journal of cachexia, sarcopenia and muscle · 2026Article
- Inhibiting HSP27 activates the XBP1s/CerS1 interplay, which triggers DRP1-driven mitophagy, thereby protecting against cell death and promoting the KSHV lytic cycle in primary effusion lymphoma cells.Cell death discovery · 2026Article
- Pharmacological Inhibition of SLC33A1 Promotes Endoplasmic Reticulum Hyperoxidation and Induces Adaptive IRE1/XBP1s Signaling.bioRxiv : the preprint server for biology · 2026Article
- SRSF3 promotes the generation of XBP1s to stabilize autophagy and enhance hypoxia adaptation in glioma.European journal of histochemistry : EJH · 2026Article
- A small molecule VDAC ligand inhibits ERAD and induces selective cancer cell death via disruption of calcium homeostasis.Nature communications · 2026Article
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.Frontiers in molecular biosciences · 2026Review
- The role of mitochondria-endoplasmic reticulum crosstalk in colorectal cancer.Genes & diseases · 2026Review
- Targeting the ER stress sensor IRE1 protects the liver from fibrosis through the downregulation of the proteostasis factor P4HB/PDIA1.Hepatology (Baltimore, Md.) · 2026Article
- Sanggenol L Induces Endoplasmic Reticulum Stress and Triggers Cell Apoptosis in Glioblastoma by Binding to BiP.International journal of biological sciences · 2026Article
- Improving Proteostasis of Trafficking-Deficient GABAACS chemical neuroscience · 2025Article
- The canonical ER stress IRE1α/XBP1 pathway mediates skeletal muscle wasting during pancreatic cancer cachexia.EMBO molecular medicine · 2025Article
- Unfolded protein response signaling promotes myeloid cell production and cooperates with oncogenic mutation.bioRxiv : the preprint server for biology · 2025Article
- Endo-chip laser-induced thrombus formation: a vessel-on-chip model for in vitro testing of antithrombotic agents.Blood vessels, thrombosis & hemostasis · 2025Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. However, no pharmacologic activators of this pathway identified to date are suitable for ER proteostasis remodeling through selective activation of IRE1/XBP1s signaling. Here, we use high-throughput screening to identify non-toxic compounds that induce ER proteostasis remodeling through IRE1/XBP1s activation. We employ transcriptional profiling to stringently confirm that our prioritized compounds selectively activate IRE1/XBP1s signaling without activating other cellular stress-responsive signaling pathways. Furthermore, we demonstrate that our compounds improve ER proteostasis of destabilized variants of amyloid precursor protein (APP) through an IRE1-dependent mechanism and reduce APP-associated mitochondrial toxicity in cellular models. These results establish highly selective IRE1/XBP1s activating compounds that can be widely employed to define the functional importance of IRE1/XBP1s activity for ER proteostasis regulation in the context of health and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.