# Novel dual-targeted inhibitors of EGFR and aurora kinase for lung cancer

> **NIH NIH R15** · FERRIS STATE UNIVERSITY · 2021 · $377,805

## Abstract

PROJECT SUMMARY
Small molecule EGFR inhibitors constitute the recommended therapy for EGFR-positive non-small cell lung
cancer (NSCLC). Resistance was first reported to EGFR inhibitors through mutations in the ATP pocket that was
addressed by a new generation of irreversible EGFR inhibitors. However, resistance has continued to evolve
with the more recent contributors of resistance being the L858R/T790M/C797S mutations in mEGFR+ NSCLC
and mutant KRAS signaling that bypasses EGFR inhibition in mKRAS+ NSCLC. There are currently no viable
EGFR-mediated treatments for mKRAS+ NSCLC. Our goal is to develop novel molecules that provide more
effective options to treat mKRAS+ and mEGFR+ NSCLC. Aurora kinases (AURK) are mitotic kinases involved
in centrosome maturation and separation during mitosis. In addition, aurora kinases drive tumorigenesis and
metastasis. Aurora kinase inhibitors have demonstrated improved anticancer effects when used in combination
with EGFR inhibitors in both mKRAS+ and mEGFR+ NSCLC. Thus, dual EGFR/AURK inhibition provides a
unique approach to overcome resistance to EGFR inhibitors. We have identified novel molecules with dual
EGFR/AURK inhibition in our lab. Our compounds demonstrated nanomolar to micromolar potencies against
EGFR and AURK. Additionally, our compounds demonstrated preferential inhibition of EGFR and AURK in a 96-
kinase selectivity panel. The goal of this proposal is to optimize lead molecules identified in our lab for potent
dual EGFR and AURK inhibition that would translate to enhanced antiproliferative effects in mKRAS+ and
mEGFR+ NSCLC. In Aim 1, we will synthesize novel series of compounds as analogs of our lead compounds.
We will evaluate the compounds in enzymatic assays against EGFR, mutant EGFR and aurora kinases.
Solubility will also be assessed. In Aim 2, we will evaluate potent dual EGFR/AURK inhibitors identified from Aim
1 for anticancer effects in mKRAS+ and mEGFR+ NSCLC and toxic effects in normal lung cells. In Aim 3, we
will investigate selectivity for dual EGFR/AURK inhibition versus off-target kinases and metabolic stability for
potent dual EGFR/AURK inhibitors identified from Aim 2.

## Key facts

- **NIH application ID:** 10114803
- **Project number:** 1R15CA246256-01A1
- **Recipient organization:** FERRIS STATE UNIVERSITY
- **Principal Investigator:** Sonali Kurup
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,805
- **Award type:** 1
- **Project period:** 2021-01-08 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114803

## Citation

> US National Institutes of Health, RePORTER application 10114803, Novel dual-targeted inhibitors of EGFR and aurora kinase for lung cancer (1R15CA246256-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10114803. Licensed CC0.

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