ArticleJCI insight2019
ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05730283 (Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention of Drug-Induced Hearing Loss in Patients Receiving Intravenous Amikacin Therapy for Non-Tuberculous Mycobacterium Disease), which is not on this map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention of Drug-Induced Hearing Loss in Patients Receiving Intravenous Amikacin Therapy for Non-Tuberculous Mycobacterium Disease
Who cites it
58 citing papers in PubMed, 74 citations in OpenAlex.
- Small Molecule Therapeutic Approaches With a Greater Focus on Hearing Loss: A Review.Health science reports · 2026Article
- Discovery of a Novel Non-MET-Mediated Otoprotective Compound Against Aminoglycoside-Induced Ototoxicity.bioRxiv : the preprint server for biology · 2026Article
- Cancer therapy-induced ototoxicity: Current challenges and emerging management strategies.Animal models and experimental medicine · 2026Review
- The aryl hydrocarbon receptor is expressed in non-sensory cells in the cochlea and regulates hair cell survival.Frontiers in molecular neuroscience · 2026Article
- Engineered Inner Ear Drug Delivery Systems for Hearing Loss Treatment.Research (Washington, D.C.) · 2026Review
- Multilevel Screening Platform Utilizing Cellular and Zebrafish Models to Identify Short Peptides with High Improvement of Motor Neuron Growth.International journal of molecular sciences · 2025Article
- Experimental and Clinical Approaches to Preventing Aminoglycoside-Induced Ototoxicity: A Scoping Review.Antioxidants (Basel, Switzerland) · 2025Review
- Comparative Antioxidant Protection of Cochlear Hair Cells from Ototoxins.Molecules (Basel, Switzerland) · 2025Article
- Rational Design of Inner Ear Drug Delivery Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- 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
- Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aminoglycoside induces RIPOR2 translocation and phosphatidylserine externalization via distinct mechanisms.Frontiers in cellular neuroscience · 2025Article
- Paving the way for better ototoxicity assessments in cisplatin therapy using more reliable animal models.Frontiers in cellular neuroscience · 2025Article
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Protective effects of MET channels on aminoglycosides- and cisplatin-induced ototoxicity.International journal of medical sciences · 2025Review
- Protective Effects of Fasudil Against Cisplatin-Induced Ototoxicity in Zebrafish: An In Vivo Study.International journal of molecular sciences · 2024Article
- Endolymphatic hydrops and cochlear synaptopathy after noise exposure are distinct sequelae of hair cell stereociliary bundle trauma.Scientific reports · 2024Article
- Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024Review
- Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice.Science translational medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins.
Indexed as
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.