Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/29883
Title: ENGINEERING NOVEL COMPOUNDS AS SPHINGOSINE KINASE INHIBITORS
Authors: WONG LINGKAI
Keywords: Inhibitor, Sphingosine Kinase, SAR Studies
Issue Date: 13-Jun-2011
Source: WONG LINGKAI (2011-06-13). ENGINEERING NOVEL COMPOUNDS AS SPHINGOSINE KINASE INHIBITORS. ScholarBank@NUS Repository.
Abstract: Sphingolipid-metabolizing enzymes control the critical balance of the cellular levels of sphingolipids, including the apoptotic inducing ceramide (Cer) and the proliferative inducing sphingosine 1-phosphate (S1P). Many evidences indicate that sphingosine kinases (SphKs) play a critical role in regulating cellular processes in the body but pharmacological inhibition of SphK has been somehow an untested field due to lack of research into development of inhibitors of SphK. The presence of two isoforms of SphK also complicated the development process as current inhibitors of SphKs were non-specific. In this project, a number of novel and specific inhibitors of human recombinant SphKs were identified and these compounds demonstrated inhibition of SphKs at micromolar concentrations. A structure activity relationship (SAR) study was also conducted to identify the key functionalities that give rise to inhibitory activity. A fluorescence method for testing the effectiveness of SphK inhibitors was developed to enhance the process in identifying potential specific SphK inhibitors.
URI: http://scholarbank.nus.edu.sg/handle/10635/29883
Appears in Collections:Ph.D Theses (Open)

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