# Designing new aminoglycosides to alleviate inner ear toxicity

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $592,155

## Abstract

   
DESCRIPTION (provided by applicant): Aminoglycosides are a widely used broad spectrum antibiotic. A major side effect of these compounds is oto- (and vestibulo) and nephrotoxicity. Data obtained during an R21 award demonstrates that these compounds enter sensory hair cells of the inner ear via a specialized mechanosensitive ion channel in vitro. Using our unique knowledge of the biophysical properties of the mechanotransduction channel coupled with insights provided by crystallography data that identifies aminoglycoside interacting sites on the bacterial ribosome, we have developed novel compounds that greatly reduced oto- and nephrotoxicity in vivo, though at some cost to the breadth of antimicrobial activity. These proof-of-principal experiments serve as the basis for iteratively designing new compounds. The design component has three phases, first to use our initial screen as a starting point where we will alter
the substituted group on sisomicin to try to better separate antimicrobial activity and the toxic side effects. Second we will synthesize and test a novel modification site based on new data arising from experiments on gentamicin derivatives. Finally, we will change the parent compound to better target specific microbes such as Pseudomonas organisms. We have developed the ability to test for purity and specificity of each compound. We can probe activity in
terms of antimicrobial function as well as oto- and nephrotoxicity in in vivo and in vitro models. We can also test for sensitivity to the development of resistance and for vestibular pathologies. Together this iterative ability based on a novel hypothesis should yield a new class of nontoxic antibiotics.

## Key facts

- **NIH application ID:** 9821204
- **Project number:** 5R01DC014720-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Alan Gi-Lun Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $592,155
- **Award type:** 5
- **Project period:** 2015-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9821204

## Citation

> US National Institutes of Health, RePORTER application 9821204, Designing new aminoglycosides to alleviate inner ear toxicity (5R01DC014720-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9821204. Licensed CC0.

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