Author(s): Michael Kezele
Mentor(s): David Michaelis, J. C. Price
Institution BYU
Sphingosine kinase 1 (SphK1) is involved in various cellular processes including cell growth, survival, migration, angiogenesis, and catalysis of the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P). Certain cancers have been shown to upregulate SphK1 and the associated pathways which lead to tumor growth, metastasis, and resistance to chemotherapy. Therefore, targeting SphK1 could be a way to slow down cancer cells growth and increase cell sensitivity to chemotherapeutic treatment. Our labs have previously shown that inhibiting SphK1 can lead to slower growth and sensitization towards other chemotherapeutic agents. The purpose of this project is to demonstrate that using a proteolysis targeting chimera (PROTAC) approach to downregulate the concentrations of SphK1 can be an effective way to slow cancer cell growth and improve response to other chemotherapeutic agents. I will describe our synthetic efforts to make new PROTACs and preliminary results towards their activity.