Wong, L., Tan, S. S.L., Lam, Y. and Melendez, A. J. (2009) Synthesis and evaluation of sphingosine analogues as inhibitors of sphingosine kinases. Journal of Medicinal Chemistry, 52(12), pp. 3618-3626. (doi: 10.1021/jm900121d)
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Publisher's URL: http://dx.doi.org/10.1021/jm900121d
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). The production of S1P, catalyzed by the action of sphingosine kinases (SPHKs), is known to be critical for many cellular processes. However, it is suggested that SPHK, and/or its catalytic product S1P, plays critical roles in various diseases including autoimmune diseases, cancer, and allergies. However, there is a great limitation of specific pharmacological inhibitors for SPHKs. In this paper, we describe a novel and stereoselective method of synthesizing SPHKs inhibitors. We generated a number of novel compounds and identified a number of specific inhibitors of human SPHKs. These compounds demonstrated inhibition of SPHKs at micromolar concentrations, making them more potent than dimethylsphingosine (DMS), a well-known inhibitor of SPHKs. In particular, one of the inhibitors was found to be selective toward a particular isoform of SPHK.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Melendez Romero, Dr Alirio |
| Authors: | Wong, L., Tan, S. S.L., Lam, Y., and Melendez, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Medicinal Chemistry |
| Journal Abbr.: | J. Med. Chem. |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| ISSN (Online): | 1520-4804 |
| Published Online: | 26 May 2009 |
| Related URLs: |
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