# Fluorinated macrocyclic peptides as BBB penetrating agent for improved GBM treatment

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $599,526

## Abstract

Project Summary/Abstract
Despite recent progress in cancer therapy, the brain tumor glioblastoma (GBM) remains an
extremely challenging disease and new therapies are badly needed. One of the biggest
obstacles to effective treatment of GBM is the presence of the blood-brain barrier (BBB), which
prevents the passage of many drugs into the brain. The highly invasive nature of GBM means
there are always cells that remain after surgery in otherwise normal brain tissue, and these cells
are protected behind the BBB, preventing many drugs from reaching them. To address this we
have formed a collaboration between Sean Lawler’s pre-clinical GBM therapeutics group at
BWH, and Brad Pentelute’s peptide chemistry group at MIT to develop approaches to 1)
specifically target glioblastoma cells, and 2) to identify agents which will cross the BBB. Our
collaboration has identified a novel peptide (M13) modified with fluorinated linkers that penetrate
the BBB in vivo. To build on this our aims are as follows: Specific Aim 1. Investigate effects of
altered chemical properties on BBB penetration by peptides modified with fluorinated linkers.
Specific Aim 2. Examine therapeutic effects of a BBB penetrant p53/MDM2 inhibitor. Specific
Aim 3. Delivery of BBB-penetrant macrocyclic peptide-drug conjugates in glioblastoma mouse
models. Our goal is to use our findings to provide the basis for further development of improved
therapeutics and provide a platform for clinical trials for glioblastoma and potentially other
tumors of the central nervous system.

## Key facts

- **NIH application ID:** 9972944
- **Project number:** 5R01CA237063-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sean Edward Lawler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,526
- **Award type:** 5
- **Project period:** 2019-07-04 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972944

## Citation

> US National Institutes of Health, RePORTER application 9972944, Fluorinated macrocyclic peptides as BBB penetrating agent for improved GBM treatment (5R01CA237063-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972944. Licensed CC0.

---

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