# Developing methionyl tRNA synthetase inhibitors as therapeutics for Chagas disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $733,618

## Abstract

Project Summary
In this project, inhibitors of the enzyme methionyl-tRNA synthetase from the protozoan parasite Trypanosoma
cruzi will be optimized to develop new drug candidates for Chagas disease. The available treatments for
Chagas disease are highly toxic and not fully efficacious, especially for the chronic stage. They need to be
replaced with safer and more effective drugs to treat the millions of people, mainly in Latin America, afflicted by
Chagas disease. The proposed research is based on the strong preliminary data of methionyl-tRNA synthetase
inhibitors from multiple chemical scaffolds showing nanomolar potency against T. cruzi cells, low toxicity to
mammalian cells, oral availability, and potent activity in murine infection models. We have chosen two
chemical scaffolds for lead optimization. Pre-defined criteria will be used to advance compounds through a
rigorous screening cascade, and the results will continually be fed back into the iterative design and synthesis
process. The goal for this project is to identify one preclinical candidate and at least one backup compound
that are ready for comprehensive GLP preclinical pharmacology and toxicology studies for further
development.

## Key facts

- **NIH application ID:** 10132983
- **Project number:** 5R01AI152358-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Frederick Simmons Buckner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $733,618
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132983

## Citation

> US National Institutes of Health, RePORTER application 10132983, Developing methionyl tRNA synthetase inhibitors as therapeutics for Chagas disease (5R01AI152358-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132983. Licensed CC0.

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