The Effect of Next-Generation Menin-MLL Inhibitors on Glioblastoma Cell Lines

Conference Year

January 2020

Abstract

Glioblastoma is the most common primary malignant brain tumor in adults. The current inability to effectively control or cure glioblastoma necessitates research into new treatments. This study focuses on the in vitro effectiveness of recently developed menin inhibitor drugs on two human-derived glioblastoma cell lines, and isogenic Neural Stem Cells (NSC). The next-generation menin-MLL inhibitor drugs that were used in this study are MI-503 and MI-1481. These drugs inhibit the menin-MLL interaction by strong binding at various pockets of the menin proteins. Treatment with MI-503 and MI-1481 was effective on both glioblastoma cell lines and the isogenic normal NSC’s. The effectiveness of these drugs was tested through cell culture assays that tested cell viability of the glioblastoma cell lines and isogenic normal NSC controls. It is still unclear how menin inhibition impacts glioblastoma tumors, but this study provides evidence that there is a potential for the menin-MLL interaction to serve as a future therapeutic target of glioblastoma.

Primary Faculty Mentor Name

Mathias Brewer

Faculty/Staff Collaborators

Albert Kim (Principal Investigator)

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Biochemistry

Primary Research Category

Biological Sciences

Abstract only.

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The Effect of Next-Generation Menin-MLL Inhibitors on Glioblastoma Cell Lines

Glioblastoma is the most common primary malignant brain tumor in adults. The current inability to effectively control or cure glioblastoma necessitates research into new treatments. This study focuses on the in vitro effectiveness of recently developed menin inhibitor drugs on two human-derived glioblastoma cell lines, and isogenic Neural Stem Cells (NSC). The next-generation menin-MLL inhibitor drugs that were used in this study are MI-503 and MI-1481. These drugs inhibit the menin-MLL interaction by strong binding at various pockets of the menin proteins. Treatment with MI-503 and MI-1481 was effective on both glioblastoma cell lines and the isogenic normal NSC’s. The effectiveness of these drugs was tested through cell culture assays that tested cell viability of the glioblastoma cell lines and isogenic normal NSC controls. It is still unclear how menin inhibition impacts glioblastoma tumors, but this study provides evidence that there is a potential for the menin-MLL interaction to serve as a future therapeutic target of glioblastoma.