Jin-Wook Kim, Yong-Woo Kim, Yuichi Inagaki, You-A Hwang, Susumu Mitsutake, Yeon-Woo Ryu, Won Koo Lee, Hyun-Joon Ha, Chang-Seo Park and Yasuyuki Igarashi

 

 

Sphingosine 1-phosphate (S1P), a product of sphingosine kinases (SphK), mediates diverse biological processes such as cell differentiation, proliferation, motility, and apoptosis. In an effort to search and identify specific inhibitors of human SphK, the inhibitory effects of synthetic sphingoid analogs on kinase activity were examined. Among the analogs tested, we found two, SG12 and SG14, that have specific inhibitory effects on hSphK2. N,N-Dimethylsphingosine (DMS), a well-known SphK inhibitor, displayed inhibitory effects for both SphK1 and SphK2, as well as protein kinase C. In contrast, SG12 and SG14 exhibited selective inhibitory effects on hSphK2. Furthermore, SG14 did not affect PKC. In isolated platelets, SG14 blocked the conversion of sphingosine into sphingosine 1-phosphate significantly. This is the first report on the identification of a hSphK2-specific inhibitor, which may provide a useful tool for studying the biological functions of hSphK2.

 

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List of Articles
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85 65. A formal synthesis of (-)-swainsonine from a chiral aziridine - Tetrahedron Lett. 2010, 51, 3284 imagefile aziridine 2010-05-29 4538
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81 41. Preparation of 2,3-diaminopropionate from ring opening of aziridine-2-carboxylate - Tetrahedron Lett. 2005, 46, 4407 imagefile aziridine 2010-05-12 4255
80 67. Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation-BMCL, 2008, 18, 5591-5593 imagefile aziridine 2010-09-27 4240
79 66. An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles from common chiral aziridines - Tetrahedron, 2010, 66, 8108-8114 imagefile aziridine 2010-09-08 4216
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72 57. Preparation of enantiopure 2-acylazetidines and their reactions with chloroformates - Tetrahedron Lett. 2007 48 269-271 imagefile aziridine 2010-05-17 3923
71 52. Sphingosine 1-phosphate (S1P) induces shape change in rat C6 glioma cells through the S1P2 receptor: development of an agonist for S1P receptors - Journal of Pharmacy and Pharmacology 2007, 59, 1035-1041 imagefile aziridine 2010-05-12 3904
70 62. Molecular docking study of aminoacyl-tRNA synthetases with ligand molecules from four different scaffolds - Bull.Kor.Chem.Soc 2010, 606 imagefile aziridine 2010-05-29 3898
69 56. Selective reduction of C-C double bonds of 2-vinylaziridines:preparation of enantiomerically pure 2-alkylaziridines - Bull. Kor. Chem. Soc. 2009, 3123 imagefile aziridine 2010-05-12 3829
68 44. Addition reactions to chiral aziridine-2-carboxaldimine toward various enantiopure nitrogen-containing heterocycles - Tetrahedron. 2005, 9281 imagefile aziridine 2010-05-12 3828
67 46. Cyclo(Phe-Pro) Modulates the Expression of ompU in Vibrio spp. - Journal of Bacteriology 2006, 188, 6, 2214 imagefile aziridine 2010-05-12 3826
66 54. The preparation of stable aziridinium ions and their ring-openings - Chem. Comm. 2008, 4363–4365 imagefile aziridine 2010-05-12 3823
65 48. Ring opening of 2-acylaziridines by acid chlorides - Tetrahedron 2006, 62, 8844-8849 imagefile aziridine 2010-05-12 3784
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62 33. A Novel Synthesis of 5-Functionalized Oxazolidin-2-ones from Enantiomerically Pure 2-Substituted N-[(R)-(+)-r-Methylbenzyl]aziridines - J. Org. Chem. 2003, 68, 104 imagefile aziridine 2010-05-12 3704
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60 34. Hightlights of the Chemistry of Enantiomerically Pure Aziridine-2-Carboxylates - Aldrichimica Acta 2003, 36, 57 imagefile aziridine 2010-05-12 3674
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