# Pharmacology Core

> **NIH NIH U19** · MAYO CLINIC ROCHESTER · 2021 · $209,040

## Abstract

PROJECT DESCRIPTION/ABSTRACT – PHARMACOLOGY CORE
 The Pharmacology Core will work closely with the project teams and the Therapy Evaluation Core to provide
comprehensive pharmacology support for all proposed studies. The studies supported by the Pharmacology
Core will address key pharmacologic issues and will inform crucial “go-no go” decisions in novel drug
development for GBM, including issues surrounding blood-brain barrier (BBB). Understanding the ability of drugs
to distribute across the BBB into tumor tissue and surrounding ‘normal’ brain infiltrated by GBM cells is critically
important for the development of effective therapies, especially those treatments that could lead to long-term
survival. The proposed Center projects are focused on developing combinatorial regimens using DNA damage
response (DDR) inhibitors targeting the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR)
signaling pathways (Project 1) or the p53/murine-double minute 2 (MDM2) pathway (Project 2). Efficacy of these
combination strategies is dependent on adequate drug exposure at optimal times throughout the tumor volume,
including the infiltrative regions. Further, both projects will use a rigorous spatial evaluation of pharmacokinetic
(PK) processes and resulting pharmacodynamic (PD) effects of these drugs within normal brain and throughout
brain tumor tissues to design and implement the most efficacious combination regimens. The Pharmacology
Core is led by Dr. William Elmquist, who is a Professor of Pharmaceutics at the University of Minnesota and a
world expert in the PK of drug distribution across the blood-brain barrier (BBB) into normal brain and brain
tumors. His key co-investigators include Dr. Forest White from Massachusetts Institute of Technology and Dr.
Nathalie Agar from Harvard University. These three research groups have an extensive collaborative history,
and many of the strategies planned have been rigorously validated through this close collaboration across the
three laboratories. The specific functions of this Pharmacology Core can be divided into three specific Aims:
Specific Aim 1: Pharmacokinetic and CNS distribution analyses of novel therapeutic agents
Specific Aim 2: Support the development of pharmacodynamic biomarkers
Specific Aim 3: Support human Phase 0/1 clinical trial development

## Key facts

- **NIH application ID:** 10305364
- **Project number:** 1U19CA264362-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** William Elmquist
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,040
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10305364

## Citation

> US National Institutes of Health, RePORTER application 10305364, Pharmacology Core (1U19CA264362-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10305364. Licensed CC0.

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