ArticleNature chemical biology2012
Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
119 citing papers in PubMed, 190 citations in OpenAlex.
- A patent perspective of RSK inhibitors to treat cancer (2020-present).Expert opinion on therapeutic patents · 2026Review
- Pyrazolylpyrimidinamines Decorated via Petasis Reaction as Small-Molecule Activators of the RNA-Degrading Ribonuclease IRE1α.ACS bio & med chem Au · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- A systematic review on the potential of modulating the IRE arm of the UPR in U87 and U251 glioblastoma cells for improved therapeutic efficacy.Molecular biology research communications · 2026Review
- Harnessing indole scaffolds to identify small-molecule IRE1α inhibitors modulating XBP1 mRNA splicing.Nature communications · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Modulation of Endoplasmic Reticulum Stress in Experimental Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.ACS chemical biology · 2025Article
- Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors.Cell communication and signaling : CCS · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Discovery of a Compound That Inhibits IRE1αACS chemical biology · 2024Article
- Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.The Journal of biological chemistry · 2024Article
- Dual RNase activity of IRE1 as a target for anticancer therapies.Journal of cell communication and signaling · 2023Review
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.Biomedicines · 2023Review
- Article
- Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury.Molecules (Basel, Switzerland) · 2023Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Under endoplasmic reticulum stress, unfolded protein accumulation leads to activation of the endoplasmic reticulum transmembrane kinase/endoRNase (RNase) IRE1α. IRE1α oligomerizes, autophosphorylates and initiates splicing of XBP1 mRNA, thus triggering the unfolded protein response (UPR). Here we show that IRE1α's kinase-controlled RNase can be regulated in two distinct modes with kinase inhibitors: one class of ligands occupies IRE1α's kinase ATP-binding site to activate RNase-mediated XBP1 mRNA splicing even without upstream endoplasmic reticulum stress, whereas a second class can inhibit the RNase through the same ATP-binding site, even under endoplasmic reticulum stress. Thus, alternative kinase conformations stabilized by distinct classes of ATP-competitive inhibitors can cause allosteric switching of IRE1α's RNase--either on or off. As dysregulation of the UPR has been implicated in a variety of cell degenerative and neoplastic disorders, small-molecule control over IRE1α should advance efforts to understand the UPR's role in pathophysiology and to develop drugs for endoplasmic reticulum stress-related diseases.
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What OpenQuestion holds
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.