ArticleJCI insight2021
Identification of a series of hair-cell MET channel blockers that protect against aminoglycoside-induced ototoxicity.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- SKOOTS: Skeleton-Oriented Object Segmentation for Mitochondria in High-Resolution Cochlear EM Datasets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TRPV4 mediates aminoglycoside trafficking and ototoxicity without compromising antimicrobial efficacy.Cell death discovery · 2026Article
- Spontaneous calcium transients in hair cell stereocilia.Scientific reports · 2025Article
- SKOOTS: Skeleton-oriented object segmentation for mitochondria.bioRxiv : the preprint server for biology · 2025Article
- Vernonia amygdalina displays otoprotective effects via antioxidant pathway on cisplatin-induced hair cell loss in zebrafish.Archives of toxicology · 2025Article
- Identification of druggable binding sites and small molecules as modulators of TMC1.Communications biology · 2025Article
- Protective effects of MET channels on aminoglycosides- and cisplatin-induced ototoxicity.International journal of medical sciences · 2025Review
- Endolymphatic hydrops and cochlear synaptopathy after noise exposure are distinct sequelae of hair cell stereociliary bundle trauma.Scientific reports · 2024Article
- Chemical screen in zebrafish lateral line identified compounds that ameliorate neomycin-induced ototoxicity by inhibiting ferroptosis pathway.Cell & bioscience · 2024Article
- Calcium channel inhibitor and extracellular calcium improve aminoglycoside-induced hair cell loss in zebrafish.Archives of toxicology · 2024Article
- Large-scale annotated dataset for cochlear hair cell detection and classification.Scientific data · 2024Article
- Article
- Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway.Journal of the Chinese Medical Association : JCMA · 2024Review
- A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 signalling pathway in zebrafish embryos.Basic & clinical pharmacology & toxicology · 2023Article
- Large-scale annotated dataset for cochlear hair cell detection and classification.bioRxiv : the preprint server for biology · 2023Article
- The hair cell analysis toolbox is a precise and fully automated pipeline for whole cochlea hair cell quantification.PLoS biology · 2023Article
- Charge and lipophilicity are required for effective block of the hair-cell mechano-electrical transducer channel by FM1-43 and its derivatives.Frontiers in cell and developmental biology · 2023Article
- Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity.Frontiers in cell and developmental biology · 2023Review
- Ancillary treatment of patients with lung disease due to non-tuberculous mycobacteria: a narrative review.Journal of thoracic disease · 2022Review
- Chronic neurotransmission increases the susceptibility of lateral-line hair cells to ototoxic insults.eLife · 2022Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
To identify small molecules that shield mammalian sensory hair cells from the ototoxic side effects of aminoglycoside antibiotics, 10,240 compounds were initially screened in zebrafish larvae, selecting for those that protected lateral-line hair cells against neomycin and gentamicin. When the 64 hits from this screen were retested in mouse cochlear cultures, 8 protected outer hair cells (OHCs) from gentamicin in vitro without causing hair-bundle damage. These 8 hits shared structural features and blocked, to varying degrees, the OHC's mechano-electrical transducer (MET) channel, a route of aminoglycoside entry into hair cells. Further characterization of one of the strongest MET channel blockers, UoS-7692, revealed it additionally protected against kanamycin and tobramycin and did not abrogate the bactericidal activity of gentamicin. UoS-7692 behaved, like the aminoglycosides, as a permeant blocker of the MET channel; significantly reduced gentamicin-Texas red loading into OHCs; and preserved lateral-line function in neomycin-treated zebrafish. Transtympanic injection of UoS-7692 protected mouse OHCs from furosemide/kanamycin exposure in vivo and partially preserved hearing. The results confirmed the hair-cell MET channel as a viable target for the identification of compounds that protect the cochlea from aminoglycosides and provide a series of hit compounds that will inform the design of future otoprotectants.
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