# Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment

> **NIH NIH R16** · ST. JOHN'S UNIVERSITY · 2024 · $164,000

## Abstract

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.

## Key facts

- **NIH application ID:** 10837849
- **Project number:** 5R16GM145557-03
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **Principal Investigator:** Vikas Vasudeo Dukhande
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2022-05-11 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837849

## Citation

> US National Institutes of Health, RePORTER application 10837849, Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment (5R16GM145557-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10837849. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*