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
번호 제목 글쓴이 날짜 조회 수
58 58. Asymmetric formal synthesis of (-)-formoterol and (-)-tamsulosin - Heterocycles - 2007, 2243 imagefile aziridine 2010-05-29 5166
57 57. Preparation of enantiopure 2-acylazetidines and their reactions with chloroformates - Tetrahedron Lett. 2007 48 269-271 imagefile aziridine 2010-05-17 4192
56 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 4129
55 55. Dynamic Thermodynamic Resolution:Advantage by Separation of Equilibration and Resolution - Acc. Chem. Res., 2009, 42, 224 imagefile aziridine 2010-05-12 3476
54 54. The preparation of stable aziridinium ions and their ring-openings - Chem. Comm. 2008, 4363–4365 imagefile aziridine 2010-05-12 4097
53 53. Nucleophilic substitution of (sulfonyloxymethyl)aziridines: an asymmetric synthesis of both isomers of mexiletine - Tetrahedron 2008, 64, 11110 imagefile aziridine 2010-05-12 3496
52 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 4167
51 51. Selective Mono-BOC Protection of diamines - Synth. Comm. 2007, 37, 737-742 imagefile aziridine 2010-05-12 5223
50 50. Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Aβ fibril formation - Bioorg. Med. Chem. Lett. 2007, 17, 1466-1470 imagefile aziridine 2010-05-12 3397
49 49. Dihydroxylation of 2-vinyl-aziridine: Efficient synthesis of D-ribo-phytosphingosine - Chem. Commun. 2007, 79-81 imagefile aziridine 2010-05-12 4012
48 48. Ring opening of 2-acylaziridines by acid chlorides - Tetrahedron 2006, 62, 8844-8849 imagefile aziridine 2010-05-12 4050
47 47. An efficient synthesis of chiral terminal 1,2-diamines using an enantiomerically pure [1-(10R)-methylbenzyl]aziridine-2-yl]methanol - Tetrahedron 2006, 62, 8393-8397 imagefile aziridine 2010-05-12 3461
46 46. Cyclo(Phe-Pro) Modulates the Expression of ompU in Vibrio spp. - Journal of Bacteriology 2006, 188, 6, 2214 imagefile aziridine 2010-05-12 4097
45 45. Synthesis of constrained ceramide analogs and their potent antileukemic activities - Bioorg. Med. Chem. Lett. 2006, 16, 1880-1883 imagefile aziridine 2010-05-12 4474
44 44. Addition reactions to chiral aziridine-2-carboxaldimine toward various enantiopure nitrogen-containing heterocycles - Tetrahedron. 2005, 9281 imagefile aziridine 2010-05-12 4077
43 43. Synthesis of Functionalized Bicyclic Triazoles from Chiral Aziridines - Synlett. 2005, 14, 2187 imagefile aziridine 2010-05-12 4382
42 42. Lewis acid-catalyzed stereospecific ring expansion of aziridine-2-carboxylates to imidazolidin-2-ones - Chem. Commun. 2005, 24, 3062 imagefile aziridine 2010-05-12 3768
41 41. Preparation of 2,3-diaminopropionate from ring opening of aziridine-2-carboxylate - Tetrahedron Lett. 2005, 46, 4407 imagefile aziridine 2010-05-12 4509
» 40. Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases - Bioorg. Med. Chem. 2005, 13, 3475 imagefile aziridine 2010-05-12 3982
39 39. Stereoselective Addition of Nucleophiles to Aziridinyl-2-carboxaldimine - Bull. Kor. Chem. Soc. 2004, 1617 imagefile aziridine 2010-05-12 3530
38 38. Synthesis and antibacterial activity of arylpiperazinyl oxazolidinones with diversification of the N-substituents - Bioorg. Med. Chem. 2004, 3881 imagefile aziridine 2010-05-12 3744
37 37. Highly Stereoselective Addition of Organomagnesium Reagents to Aziridinyl-2-carboxaldimine: Preparation of Enantiopure 2-Aminomethylaziridines and 4,5-Disubstituted Imidazolidin-2-ones - Synlett. 2004, 489 imagefile aziridine 2010-05-12 3547
36 36. Dicyano{[(1S)-(1-phenylethyl)aziridine-2-yl]methanolato-κ2N,O}boron - Acta Cryst. (2003). C59, 0659-0660 imagefile aziridine 2010-05-12 3484
35 35. Efficient Synthesis of Enantiomerically Pure 2-Acylaziridines - J. Org. Chem. 2003, 68, 7675 imagefile aziridine 2010-05-12 3473
34 34. Hightlights of the Chemistry of Enantiomerically Pure Aziridine-2-Carboxylates - Aldrichimica Acta 2003, 36, 57 imagefile aziridine 2010-05-12 3899
33 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 3966
32 32. Novel Stereoselective Synthesis of Functionalized Oxazolidinones from Chiral Aziridines - J. Org. Chem. 2003, 68, 43 imagefile aziridine 2010-05-12 3404
31 31. Facile synthesis of β-anilinopropionates from lewis acid-induced N-methyleneanilines with ketene acetals - Syn. Comm. 2002, 32, 1495 imagefile aziridine 2010-05-12 3357
30 30. An Efficient Synthesis of N-Boc-D-Diphenylalanine from A Chiral Aziridine-2-Carboxylate - Heterocycles 2002, 57, 1143 imagefile aziridine 2010-05-12 3665
29 29. Syntheses of 1b -Methylcarbapenems Bearing 5-Methyl-4-hydroxypyrrolidinone - Chem. Pharm. Bull. 2002, 50, 415 imagefile aziridine 2010-05-12 3427


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