# Drug Discovery for Chagas Disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $837,654

## Abstract

Project Summary
The long-term objective of the proposed research is to develop a new drug for Chagas disease,
an infectious disease caused by the parasite Trypanosoma cruzi. Chagas disease is estimated
to effect 6-8 million people, mainly in Latin America. The work is motivated by the inadequacy of
current therapies with respect to their poor efficacy and tolerability. In this new application we
will focus on two chemical scaffolds that were discovered in the hit-to-lead project from a
previous NIH supported project. The current lead compounds have potent anti-trypanosomal
activity (single or double-digit nanomolar range), good metabolic stability, wide-therapeutic
window, and chemical tractability. Safety screens have been reassuring. With further
optimization, the goal is to identify at least one final candidate to nominate for clinical
development for Chagas disease. In the research plan, the two compound series will have
specific issues addressed such as improving solubility, metabolic stability, or other
characteristics. The approach will employ classic medicinal chemistry and iterative rounds of
compound design, synthesis, and testing. With >200 compounds already made for each of the
scaffolds, we have detailed structure activity relationships (SAR) to guide ongoing work. The
target is known for one of the compound series (the trypanosome proteasome), and two
experimental approaches are planned to identify the target of the other compound series.
Compound testing will include in vitro assays for anti-trypanosomal activity, mammalian cell
cytotoxicity, solubility, mouse pharmacokinetics, and murine efficacy models following a
screening cascade with defined go/no-go criteria. Safety studies and rat toxicology studies will
be done towards the end of the funding period on the final lead candidates. At the end of this
four-year project, at least one drug candidate will be selected for late-stage preclinical
development for Chagas disease.

## Key facts

- **NIH application ID:** 10398001
- **Project number:** 5R01AI147504-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Frederick Simmons Buckner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $837,654
- **Award type:** 5
- **Project period:** 2019-05-09 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398001

## Citation

> US National Institutes of Health, RePORTER application 10398001, Drug Discovery for Chagas Disease (5R01AI147504-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10398001. Licensed CC0.

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