biostudies-literatureZallocchi MCreighton UniversityNIDCD NIH HHSU.S. Army Medical Research and Materiel CommandDepartment of Defense United StatesOffice of Naval ReactorsNational Institutes of HealthBellucci Foundation141561https://www.ebi.ac.uk/biostudies/studies/S-EPMC8021103biostudies-literatureUnknown6(5)Hair cell loss is the leading cause of hearing and balance disorders in humans. It can be caused by many factors, including noise, aging, and therapeutic agents. Previous studies have shown the therapeutic potential of quinoxaline against drug-induced ototoxicity. Here, we screened a library of 68 quinoxaline derivatives for protection against aminoglycoside-induced damage of hair cells from the zebrafish lateral line. We identified quinoxaline-5-carboxylic acid (Qx28) as the best quinoxaline derivative that provides robust protection against both aminoglycosides and cisplatin in zebrafish and mouse cochlear explants. FM1-43 and aminoglycoside uptake, as well as antibiotic efficacy studies, revealed that Qx28 is neither blocking the mechanotransduction channels nor interfering with aminoglJCI insightCharacterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss.PMC8021103RH190050LB692RH170030R01 DC015444R01DC015444R01DC015010N00014-18-1-2507R01 DC015010Bellucci FoundationLiu HZuo JZallocchi MHati SHe DZXu ZHausman WfalseCharacterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss.Hair cell loss is the leading cause of hearing and balance disorders in humans. It can be caused by many factors, including noise, aging, and therapeutic agents. Previous studies have shown the therapeutic potential of quinoxaline against drug-induced ototoxicity. Here, we screened a library of 68 quinoxaline derivatives for protection against aminoglycoside-induced damage of hair cells from the zebrafish lateral line. We identified quinoxaline-5-carboxylic acid (Qx28) as the best quinoxaline derivative that provides robust protection against both aminoglycosides and cisplatin in zebrafish and mouse cochlear explants. FM1-43 and aminoglycoside uptake, as well as antibiotic efficacy studies, revealed that Qx28 is neither blocking the mechanotransduction channels nor interfering with aminogl2021-01-01T00:00:00Z2021 Mar2026-05-08T03:21:20.021Z2026-05-01T03:05:38.269ZS-EPMC80211033347630610.1172/jci.insight.141561