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Honors Theses

Colby College

Pharmaceutical Preparations

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Development Of A Chemical Genetic Screen To Identify Compounds That Enhance Laromustine Cytotoxicity, Xiaoou Wang Jan 2019

Development Of A Chemical Genetic Screen To Identify Compounds That Enhance Laromustine Cytotoxicity, Xiaoou Wang

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials against acute myeloid leukemia. Though laromustine showed some success in clinical trials, more experiments are needed to understand the hematological toxicity and the molecular mechanisms of patients’ resistance. This project aims to develop a strategy to identify compounds synergistic with laromustine in cultured leukemia cells from a library of 450 FDA-approved compounds through a forward chemical genetic screen. To optimize the screen, the cell seeding density, doubling time, and dose response curves were determined. The optimized concentration of HL60 cells in these experiments was determined to be between 25,000 and …


Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks Jan 2016

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

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 …