# The design, synthesis, and characterization of potent and selective MEK7 inhibitors as targeted therapies for T-cell acute lymphoblastic leukemia

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2021 · $49,354

## Abstract

Project Summary
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients and
the most frequent cause of cancer-related mortality before the age of 20. Current treatment strategies act by
non-specific mechanisms that are incapable of achieving and maintaining remission in the nearly 1 out of 4
pediatric patients with therapy-resistant disease. While targeted therapies are not currently available for ALL
patients, they could potentially improve patient outcomes by interfering with pathological cellular and molecular
activities that facilitate resistance to multi-agent chemotherapy. Increased expression of protein kinase MEK7
and consequent amplification of downstream MAP kinase signaling have been identified as two such processes
facilitating chemoresistance in T-cell ALL (T-ALL), rendering MEK7 an attractive target for T-ALL directed
therapies. Unfortunately, there are no small molecules known to potently and selectively inhibit this MEK
isoform. Leveraging our published platform for interrogating inhibitor selectivity across the MEK kinase family,
we have designed and synthesized a lead compound exhibiting potent MEK7 inhibition. The objective of my
present proposal is the further development and optimization of a potent and selective small molecule MEK7
inhibitor to chemically probe aberrant signaling in this arm of the MAPK pathway in T-ALL models. Our
methodology entails a multifaceted approach employing strategies from disciplines spanning computational
chemistry, organic synthesis, protein biochemistry, and molecular biology. Through these complementary
modalities, we seek to gain new insight into the roles of the least understood MEK isoform in the molecular
pathophysiology underlying T-ALL. Of utmost clinical significance, the studies in this proposal will survey the
efficacy of direct MEK7 inhibitors as targeted therapies for T-ALL.

## Key facts

- **NIH application ID:** 10061570
- **Project number:** 5F31CA228431-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Dalton Robert Kim
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $49,354
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-03-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10061570

## Citation

> US National Institutes of Health, RePORTER application 10061570, The design, synthesis, and characterization of potent and selective MEK7 inhibitors as targeted therapies for T-cell acute lymphoblastic leukemia (5F31CA228431-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10061570. Licensed CC0.

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