Development of a Chemical Genetic Screen to Determine Synergistic Compounds with Laromustine in Treating Glioblastoma Multiforme Cultured Cells
Date of Award
Honors Thesis (Open Access)
Colby College. Chemistry Dept.
Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM cells was found to be 6 hours; causing acute cell death in half as much time as the treatment with a lethal dose of Temozolomide, the current GBM treatment. The LD50 for laromustine in cultured GBM cells was observed to be approximately 700 μM when treated for 6 hours. Using these standards of optimization for maximum reproducibility, a chemical genetic screen will be used to determine the synergistic effects of laromustine with a library of characterized small molecules.
laromustine, temozolomide, glioblastoma multiforme, chemical genetic screen
Recommended CitationWeeks, Ryan, "Development of a Chemical Genetic Screen to Determine Synergistic Compounds with Laromustine in Treating Glioblastoma Multiforme Cultured Cells" (2016). Honors Theses. Paper 823.
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