The Study Of Human Sphingosine Kinase And Its Potential Inhibitors

Brooke Christensen

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Chemistry

Presentation Type

Mentored

Mentor

Mentor: Christian Grattan and Jason Hurlbert, Department of Chemistry, Physics, and Geology, Winthrop University

Abstract

Stress towards cancer cells have the potential to cause the Sphingomyelin to branch off the cell membrane and enter the cell, triggering a metabolic reaction. During this reaction, the Sphingomyelin is a precursor for the proapoptotic compound, Ceramide, as well as the Sphingosine 1-Phosphate (S1P), which is known for its role in promoting cell proliferation. Sphingosine Kinase (SK) catalyzes the reaction by phosphorylating Sphingosine to produce S1P. Sphingosine, converted from Ceramide, maintains a minor role in cancerous cells and is therefore overlooked in the anticancer research. SK has recently been targeted for anticancer activity and research includes synthesizing potential SK inhibitors (SKI). An inhibitor was found to successfully inhibit SK in vitro; however, its high Log P value disallowed it to be successful in vivo. The SKI’s Log P value, a ratio that inversely corresponds to the compounds solubility, is around six. The desired range for drugs for the human body is below five. It was hypothesized that a modification to the functional group of a carbonyl group and hydroxyl group of the SKI would increase the solubility of the inhibitor compound, therefor decrease the Log P value to the desired range. Future work includes modifications for all the functional groups of the SKI and testing the inhibitor’s solubility.

Start Date

4-11-2015 9:00 AM

End Date

4-11-2015 9:15 AM

COinS
 
Apr 11th, 9:00 AM Apr 11th, 9:15 AM

The Study Of Human Sphingosine Kinase And Its Potential Inhibitors

Stress towards cancer cells have the potential to cause the Sphingomyelin to branch off the cell membrane and enter the cell, triggering a metabolic reaction. During this reaction, the Sphingomyelin is a precursor for the proapoptotic compound, Ceramide, as well as the Sphingosine 1-Phosphate (S1P), which is known for its role in promoting cell proliferation. Sphingosine Kinase (SK) catalyzes the reaction by phosphorylating Sphingosine to produce S1P. Sphingosine, converted from Ceramide, maintains a minor role in cancerous cells and is therefore overlooked in the anticancer research. SK has recently been targeted for anticancer activity and research includes synthesizing potential SK inhibitors (SKI). An inhibitor was found to successfully inhibit SK in vitro; however, its high Log P value disallowed it to be successful in vivo. The SKI’s Log P value, a ratio that inversely corresponds to the compounds solubility, is around six. The desired range for drugs for the human body is below five. It was hypothesized that a modification to the functional group of a carbonyl group and hydroxyl group of the SKI would increase the solubility of the inhibitor compound, therefor decrease the Log P value to the desired range. Future work includes modifications for all the functional groups of the SKI and testing the inhibitor’s solubility.