# Core B: Structure and Biochemistry

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2020 · $240,508

## Abstract

The diverse genetic alterations that drive non-small cell lung cancer (NSCLC) provide
attractive targets for therapeutic intervention, and tyrosine kinase inhibitors targeting mutant
EGFR and rearranged ALK have demonstrated considerable clinical efficacy. However,
treatment acquired resistance is a recurring theme in TKI therapy, and furthermore, current
targeted therapies are not effective in KRAS-mutant NSCLC. The central goal of this P01
program is to advance drug development for NSCLC by developing novel approaches to
targeting the kinases that drive these cancers, as well as those that facilitate the epigenetic and
transcriptional adaptation that promotes resistance to targeted therapies. The kinase targets we
focus on include mutant EGFR, c-RAF, Mek1/2, and transcription-associated cyclin dependent
kinases.
 Inhibitor discovery and optimization is much more efficient when grounded in direct
biochemical assays with purified components and when illuminated by co-crystal structures of
lead compounds. The role of the Structure and Biochemistry Core (Core B) is to support each of
the three projects by providing purified recombinant kinases, expertise in inhibitor
characterization, in vitro assays for compound binding, molecular modeling and virtual
screening, and crystallographic structure determination of kinase inhibitor complexes.
Centralizing these activities in the core will prevent duplication of effort and expertise in the
individual projects and will leverage the resources and experience available in the laboratory of
the core director. We have extensive experience in the structural biology and inhibition of
kinases and long-standing collaborative ties with the project leaders and core directors.

## Key facts

- **NIH application ID:** 10003965
- **Project number:** 5P01CA154303-09
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** MICHAEL J ECK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,508
- **Award type:** 5
- **Project period:** 2012-05-11 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003965

## Citation

> US National Institutes of Health, RePORTER application 10003965, Core B: Structure and Biochemistry (5P01CA154303-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10003965. Licensed CC0.

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