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Developing methionyl tRNA synthetase inhibitors as therapeutics for Chagas disease

Award Number: R01AI152358
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Developing methionyl tRNA synthetase inhibitors as therapeutics for Chagas disease - 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.


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 = $0 )
2025	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	4	3/31/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $814,270 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	4	3/10/2023	NON-COMPETING CONTINUATION	$814,270
														Subtotal = $814,270

Issue Date FY: 2022 ( Subtotal = $772,120 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	3	3/18/2022	NON-COMPETING CONTINUATION	$772,120
														Subtotal = $772,120

Issue Date FY: 2021 ( Subtotal = $733,618 )
2021	2021	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	2	3/15/2021	NON-COMPETING CONTINUATION	$733,618
														Subtotal = $733,618

Issue Date FY: 2020 ( Subtotal = $733,618 )
2020	2020	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	1	3/25/2020	NEW	$733,618
														Subtotal = $733,618

Grand Total All Awards = $3,053,626

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Developing methionyl tRNA synthetase inhibitors as therapeutics for Chagas disease

Award Number: R01AI152358

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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