Pharmacologic Regulation of Auditory Hair Cell Regeneration
Abstract
Post-mitotic mammalian hair cells (HCs) do not regenerate after traumatic damage, and their death leads to irreversible hearing and balance impairment. Therapeutically induced generation of new sensory HCs has been considered for many years. Nevertheless, there are no available pharmacologic alternatives to stimulate HC regeneration through controlled SC proliferation safely. Studies by our laboratory uncovered the proliferative and therapeutic potential of quinoxaline (Qx), a non-steroidal anti-inflammatory compound to regenerate lost sensorineural HCs. To improve its preclinical properties, we modified our current Qx molecule during the past year, generated several analogs (Qx1 - Qx 70), and tested them in vitro and in vivo (zebrafish). From those 70 analogs, Qx-27 showed the best medicinal chemistry profile. We have continued to modify that chemotype to expand the structure of activity relationship of this novel chemotype, identify other proliferative analogs, and optimize potency, bioavailability, and in vivo efficacy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1152709
Entities
People
- Sonia M. Rocha-sanchez
Organizations
- Creighton University