# Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $668,478

## Abstract

Abstract: Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis
Toxoplasma gondii infection is the most common known parasitic infection and causes systemic infections,
particularly severe in immunocompromised humans, that damage the central nervous system. No clear
beneficial therapy exists for pregnant women, who are experiencing new infections and possible fetal infection.
Bumped-kinase inhibitors (BKIs) target Calcium-Dependent Protein Kinase 1, necessary for cell entry and
growth of T. gondii. We have developed and shown proof-of-concept for treating Toxoplasma gondii CNS
infections and pregnancy infections with BKIs. However, our late leads still have some issues such as optimal
CNS penetration and metabolites associated with safety issues. In Aim 1 of the proposed work, we will
develop BKIs that retain high systemic concentrations and distribution to both the central nervous system
(CNS) AND the fetus with acceptable safety attributes for use in pregnancy. This work will be aided by the
extensive knowledge of our leads, computational predictions, and iterative experimentation addressing the few
remaining issues. We will elucidate the pharmacodynamics and pharmacokinetics (PK/PD) associated with
efficacious T. gondii therapy, an area that hasn’t been explored before in toxoplasmosis therapy. Once optimal
BKIs are obtained and the optimal PK/PD known, in Aim 2 we will test BKI late leads for effects in rodent and
ovine models of congenital toxoplasmosis. The pregnant mice T. gondii congenital model will be useful for
prioritizing compounds to further study in the pregnant sheep T. gondii congenital model. The pregnant sheep
T. gondii congenital model is a superior model for human T. gondii congenital therapy than the mouse model
because of similarities in sheep and humans (vs. mice) in length of gestation, numbers of fetuses per
pregnancy, similarities in outcomes of congenital infection, and immune recognition of T. gondii. Our
deliverables will be late lead BKIs, with demonstrated safety and efficacy in two animal models of congenital
toxoplasmosis, to advance to GLP toxicity testing required for IND approval. Our likelihood for success is
greatly improved by our collective knowledge from working on these compounds for cryptosporidiosis and the
well-established scientific team together with advisors and consultants from our partners at PATH, AbbVie, and
Bayer, who have decades of experience in pharmaceutical development.

## Key facts

- **NIH application ID:** 10789928
- **Project number:** 5R01HD102487-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** WESLEY C VAN VOORHIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $668,478
- **Award type:** 5
- **Project period:** 2021-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789928

## Citation

> US National Institutes of Health, RePORTER application 10789928, Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis (5R01HD102487-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10789928. Licensed CC0.

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