ArticleScience advances2021
Cork-in-bottle mechanism of inhibitor binding to mammalian complex I.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Mitochondrial complex I as a master regulator of redox signaling: From structural architecture to directionality of electron transport.Free radical biology & medicine · 2026Review
- PSG6: A mitochondrially-targeted gentisic acid derivative exerts antiplatelet action via mitochondrial complex I inhibition.Redox biology · 2026Article
- Mammalian Respiratory Chain Complex Assemblies and Their Links to Mitochondria Stress-Induced Human Diseases.Advances in experimental medicine and biology · 2026Review
- Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms.Nature structural & molecular biology · 2026Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Article
- Regulation of respiratory complex I assembly by FMN cofactor targeting.Redox biology · 2024Article
- The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors.Biology direct · 2023Article
- Mechanism of rotenone binding to respiratory complex I depends on ligand flexibility.Scientific reports · 2023Article
- Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance inActa pharmaceutica Sinica. B · 2023Article
- Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits againstACS medicinal chemistry letters · 2023Article
- Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides.Science (New York, N.Y.) · 2023Article
- Article
- Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.Nature medicine · 2023Article
- NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.Open biology · 2022Article
- Binding of Natural Inhibitors to Respiratory Complex I.Pharmaceuticals (Basel, Switzerland) · 2022Review
- cAMP/PKA Signaling Modulates Mitochondrial Supercomplex Organization.International journal of molecular sciences · 2022Article
- Respiratory complex I with charge symmetry in the membrane arm pumps protons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structure of respiratory complex I - An emerging blueprint for the mechanism.Current opinion in structural biology · 2022Review
- Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Mitochondrial complex I (NADH:ubiquinone oxidoreductase), a major contributor of free energy for oxidative phosphorylation, is increasingly recognized as a promising drug target for ischemia-reperfusion injury, metabolic disorders, and various cancers. Several pharmacologically relevant but structurally unrelated small molecules have been identified as specific complex I inhibitors, but their modes of action remain unclear. Here, we present a 3.0-Å resolution cryo-electron microscopy structure of mammalian complex I inhibited by a derivative of IACS-010759, which is currently in clinical development against cancers reliant on oxidative phosphorylation, revealing its unique cork-in-bottle mechanism of inhibition. We combine structural and kinetic analyses to deconvolute cross-species differences in inhibition and identify the structural motif of a "chain" of aromatic rings as a characteristic that promotes inhibition. Our findings provide insights into the importance of π-stacking residues for inhibitor binding in the long substrate-binding channel in complex I and a guide for future biorational drug design.
Identifiers
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.