# Synthesis, and Evaluation of Potent and Selective MEK4 Inhibitors as a Targeted Therapeutic for Metastatic Pancreatic Ductal Adenocarcinoma

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2020 · $38,801

## Abstract

Project Summary
 Pancreatic ductal adenocarcinoma (PDAC) is a deadly and common form of pancreatic cancer with an
extremely low rate of survival. Due to the lack of distinct early-stage symptoms, most patients present with
metastatic PDAC at the time of diagnosis. With limited effective treatments available for metastatic PDAC, and
surgery being the only curative treatment, the US has recently seen an increasing number of fatalities due to
PDAC. Matrix metalloproteinase-2 (MMP-2), a metalloproteinase directly associated with the development of
metastatic cancers, has been heavily studied as a therapeutic target for stopping metastasis. However, MMP-2
inhibitors have failed in clinical trials, largely due to low efficacy and high toxicity. We propose that a focus on
enzymes upstream from MMP-2 will allow for the development of more effective therapies for PDAC. Probing
one such enzyme, MEK4 (otherwise known as MAP2K4), would give crucial insight into its role in proliferating
metastatic PDAC. Increased expression of MEK4 has already been observed to increase metastasis in PDAC
in multiple in vitro and in vivo studies. Unfortunately, no chemical probes for MEK4 currently exist. Leveraging
our published platform for interrogating inhibitor selectivity across the MEK kinase family, as well as our published
work on developing an initial lead for MEK4, this proposal is focused on filling this gap. As a multidisciplinary
training platform utilizing synthetic organic chemistry, computational modeling, medicinal chemistry, in vitro
biological assays, X-ray crystallography, molecular biology, and cancer models, the studies described in this
proposal aim to provide new insights into the roles of MEK4 in regulating metastasis. Working with my sponsor,
Prof. Scheidt, will provide intensive training in chemical synthesis, while my co-sponsor, Prof. Munshi, will provide
similarly comprehensive training in cancer biology and its associated techniques. This research will be carried
out as part of a collaborative effort between the Northwestern University Department of Chemistry and the
Feinberg School of Medicine (Hematology and Oncology and Lurie Cancer Center), with further support from
outside collaborators. Through this collaborative effort, I will develop the knowledge and skills to efficiently and
effectively design experiments that bridge chemistry and biology. Ultimately, these studies will survey the efficacy
of MEK4 inhibitors as targeted therapies for PDAC.

## Key facts

- **NIH application ID:** 10067755
- **Project number:** 1F31CA250353-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ada Jade Kwong
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,801
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067755

## Citation

> US National Institutes of Health, RePORTER application 10067755, Synthesis, and Evaluation of Potent and Selective MEK4 Inhibitors as a Targeted Therapeutic for Metastatic Pancreatic Ductal Adenocarcinoma (1F31CA250353-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067755. Licensed CC0.

---

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