Tuesday, July 1, 2025 7/1/2025

Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis

Award Number: R01HD102487
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

Group Awards By:

View Award Description

Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $675,079 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	5	2/19/2025	NON-COMPETING CONTINUATION	$607,571
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	001	5	4/15/2025	NON-COMPETING CONTINUATION	$67,508
														Subtotal = $675,079

Issue Date FY: 2024 ( Subtotal = $668,478 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	4	2/21/2024	NON-COMPETING CONTINUATION	$607,707
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	001	4	5/7/2024	NON-COMPETING CONTINUATION	$60,771
														Subtotal = $668,478

Issue Date FY: 2023 ( Subtotal = $649,614 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	3	2/16/2023	NON-COMPETING CONTINUATION	$649,614
														Subtotal = $649,614

Issue Date FY: 2022 ( Subtotal = $634,016 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	2	2/25/2022	NON-COMPETING CONTINUATION	$570,612
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	001	2	4/25/2022	NON-COMPETING CONTINUATION	$63,404
														Subtotal = $634,016

Issue Date FY: 2021 ( Subtotal = $701,303 )
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Child Health and Human Development Extramural Research	000	1	3/15/2021	NEW	$701,303
														Subtotal = $701,303

Grand Total All Awards = $3,328,490

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Bumped-Kinase Inhibitor Drug Development for Toxoplasmosis

Award Number: R01HD102487

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/15/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer