# Structural biology and drug discovery targeting oncogenic EGFR and BRAF kinases

> **NIH NIH R50** · DANA-FARBER CANCER INST · 2021 · $188,413

## Abstract

Project Summary
The Eck laboratory at the Dana-Farber Cancer Institute studies the structure and regulation of oncogenic
protein kinases. We apply our unique structural and mechanistic insights in collaborative drug discovery efforts
to develop inhibitors with novel mechanisms of action and with selectivity for mutant kinases. The Research
Specialist is an expert in structural biology (primarily X-ray crystallography), protein biochemistry and ligand-
binding studies, enzyme kinetics, and computational approaches (including virtual ligand screening) and has
extensive experience applying these approaches in studies of protein kinases. She is driving our research
program in two major areas of interest: 1) development of mutant-selective inhibitors of epidermal growth factor
receptor (EGFR) mutants in lung adenocarcinoma, and 2) the structure, regulation, and mechanism of
oncogenic activation of BRAF, which is relevant to many cancers. In our studies of these kinases, we seek to
understand at a structural level how the activity of the kinase is normally regulated and how this regulation is
subverted by oncogenic mutations. With our collaborators in medicinal chemistry and cellular pharmacology,
the Research Specialist is developing inhibitors that are effective against EGFR mutants that are resistant to all
current targeted therapies, including exon 20 insertion variants of EGFR and EGFR bearing both the T790M
and C797S secondary resistance mutations. In addition, the Research Specialist is working to determine the
three-dimensional structure of intact BRAF in an autoinhibited state. This work will show how diverse
oncogenic mutations lead to BRAF activation and elucidate the mechanism by which many BRAF-targeted
drugs induce paradoxical activation of the wild type kinase. In addition, it can be expected to open new
avenues for development of BRAF inhibitors that do not exhibit paradoxical activation, and may therefore be
effective in the KIAA1549:BRAF truncation fusion found in pediatric brain cancers.

## Key facts

- **NIH application ID:** 10219986
- **Project number:** 5R50CA221830-05
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Eunyoung Park
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,413
- **Award type:** 5
- **Project period:** 2017-09-19 → 2022-07-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219986

## Citation

> US National Institutes of Health, RePORTER application 10219986, Structural biology and drug discovery targeting oncogenic EGFR and BRAF kinases (5R50CA221830-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219986. Licensed CC0.

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