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Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment

Award Number: R16GM145557
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/11/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment - PROJECT SUMMARY / ABSTRACT Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a dismal 5-year survival rate (~ 5 %). GBM metastasizes to different brain regions which makes surgical resection difficult. Despite radiation therapy and chemotherapy, the median survival timeline is dire at 15 months. The major challenges in GBM therapy include late diagnosis, metastasis, resistance to chemotherapeutics, and drug delivery issues due to blood-brain barrier. Thus, efforts towards developing novel pharmacotherapies for GBM are highly warranted. Cancer cells rewire their metabolic pathways that are intimately linked to oncogenes and tumor suppressor genes. The metabolic reprogramming confers GBM several advantages in survival, proliferation, metastasis, drug resistance, and immune evasion. In addition, recent research in the cancer metabolism field has revealed an important ‘lactate shuttle’ that explains the key role of lactate transfer from systemic circulation into tumor microenvironment. Lactate utilization is highly relevant for brain tumors such as GBM. Our long-term goal is to pharmacologically target tumor metabolic reprogramming for cancer therapy. Towards that goal, we screened a number of metabolic inhibitors in GBM cells that uncovered effectiveness of an FDA-approved antiepileptic drug stiripentol with its putative target lactate dehydrogenase. The objective of this study is to elucidate molecular mechanism and changes in cancer biology by stiripentol treatment in GBM cells and GBM in vivo models. In addition, we will study structure-activity relationships of novel derivatives identified from stiripentol scaffold to develop potent inhibitors. Additionally, formulations of stiripentol and potent lead compounds will be developed and tested in the tumor xenograft model of U87 xenografts. Our research will offer novel insights in the mechanistic pharmacology of stiripentol and can lead to the development of candidate therapeutics for GBM treatment.


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 = $164,000 )
2025	2025	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	4	4/29/2025	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2024 ( Subtotal = $164,000 )
2024	2024	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PKWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	3	5/9/2024	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2023 ( Subtotal = $164,000 )
2023	2023	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	2	5/5/2023	NON-COMPETING CONTINUATION	$164,000
														Subtotal = $164,000

Issue Date FY: 2022 ( Subtotal = $164,000 )
2022	2022	ST JOHN'S UNIVERSITY, NEW YORK	8000 UTOPIA PWY	JAMAICA	NY	11439	QUEENS	USA	Biomedical Research and Research Training	000	1	5/11/2022	NEW	$164,000
														Subtotal = $164,000

Grand Total All Awards = $656,000

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Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment

Award Number: R16GM145557

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/11/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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