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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88 1. Regiospecific Alkylation of Allylic Halides with Latent-γ-Functionality - J. Org. Chem. 1984, 49, 1838 imagefile aziridine 2010-05-06 2587
87 2. a-Lithioamine synthetic equivalents from dipole-stabilized carbaniones: The r-Boc group as an activator for a’-Lithiation of carbamates - Tetrahedron Lett. 1989, 30, 1197 imagefile aziridine 2010-05-06 2582
86 3. a-Lithioamine Synthetic Equivalents: Syntheses of Diastereoisomers from the Boc Piperidines - J. Org. Chem. 1990, 55, 2578 imagefile aziridine 2010-05-06 3110
85 4. Endocyclic Restriction Test: Evaluation of Transition-Structure Geometry for an Aryl Bromide-Alkyllithium Exchange Reaction - J. Am. Chem. Soc. 1990, 112, 1629 imagefile aziridine 2010-05-06 3152
84 5. a-Lithioamine Synthetic Equivalents: Syntheses of Diastereoisomers from Boc Derivatives of Cyclic Amines - J. Org. Chem. 1993, 58, 1109 imagefile aziridine 2010-05-06 3470
83 6. Chirospecific Synthesis of (1S,3R)-l-Amino-3-(hydroxymethyl)cyclopentane a Precursor for Carbocyclic Nucleoside Synthesis. Intramolecular Aziridine Cyclizations - J. Org. Chem. 1993, 58, 5019 imagefile aziridine 2010-05-06 3298
82 7. Regioselective N-Methyl Carbon Lithiation of N-Boc-MethylalkylaminrylamiEnxepae dient Synthesis of Unsymmetrical Amines - Tetrahedron Lett. 1994, 35, 4067 imagefile aziridine 2010-05-06 3375
81 8. Chirospecific Syntheses of Precursors of Cyclopentane and cyclopentene Carbocyclic Nucleosides by [3 + 33-Coupling and Transannular Alkylation - J. Org. Chem. 1995, 60, 4602 imagefile aziridine 2010-05-06 3493
80 9. Resiospecific reductive ring cleavage of N-substituted aziridine-2-carboxylates and an aziridine-2-methanol via catalytic hydrogenation using Pd as a catalyst - Tetrahedron Lett. 1995, 36, 8431 imagefile aziridine 2010-05-06 3423
79 10. Efficient Synthesis of Ephedra Alkaloid Analogues Using an Enantiomerically Pure N-[(R)-(+)-r-Methylbenzyl]aziridine-2-carboxaldehyde - J. Org. Chem. 1996, 61, 6183 imagefile aziridine 2010-05-06 3554
78 11. An Effcient synthesis of both enantiomers of cathinone by regioselective reductive ring opening of substituted aziridines - Tetrahedron 1996, 52, 12111 imagefile aziridine 2010-05-06 3500
77 12. Highly diastereoselective reduction of enantiomerically pure aziridino ketones - Tetrahedron 1996, 52, 12117 imagefile aziridine 2010-05-06 3475
76 13. Efficient Syntheses of (1R,2R)- and (1S,2S)-2-Amino-1-alkyl(oraryl)-1,3-propanediols by Regioselective Ring Opening of Aziridine-2-methanols - J. Org. Chem. .1997, 743 imagefile aziridine 2010-05-12 3954
75 14. A new synthetic route to (3R,4S)-3-hydroxy-4-phenylazetidin-2-one as a taxol side chain precursor - Tetrahedron : Asymmetry 1998, 9, 983 imagefile aziridine 2010-05-12 3308
74 15. Preparation of both (D)- and (L)-serinol derivatives from N-[(S)-a-methylbenzyl]-aziridine-2(S)-methanol - Heterocycles 1998, 48, 1917 imagefile aziridine 2010-05-12 3531
73 16. Synthesis of Substituted (D)-Phenylalanine Derivatives by Regioselective Reduction of Enantiomerically Pure cis-2,3-Disubstituted Aziridines - Tetrahedron Lett. 1998, 39, 9193 imagefile aziridine 2010-05-12 3701
72 17. The Thiazole Route to 2-Formyl-1β-Methylcarbapenem - Bull. Kor. Chem. Soc. 1998, 19, 1294 imagefile aziridine 2010-05-12 3479
71 18. Preparation of Cysteinol Derivatives by Highly Regioselective Ring Opening Nonactivated Chiral Aziridines by Thiols - Tetrahedron 1999, 55, 10041 imagefile aziridine 2010-05-12 3850
70 19. Stereoselective synthesis of protected threo-β-hydroxy-L-glutamic acid using a chiral aziridine - Tetrahedron : Asymmetry 2000, 11, 3283 imagefile aziridine 2010-05-12 4018
69 20. Stereoselective synthesis of enantiomerically pure D-threo-PDMP; manipulation of a core 2,3-diamino alcohol unit - Tetrahedron : Asymmetry 2000, 11, 3283 imagefile aziridine 2010-05-12 3687
68 21. Cycloaddition of Lewis Acid-Induced N-Methyleneanilines as Azadienes to 1,2-Bistrimethylsilyloxycyclobutene and Oxidative Ring Expansion to 1,2,4,5-Tetrahydro-1-benzazocine-3,6-diones - J. Org. Chem. 2000, 65, 8384 imagefile aziridine 2010-05-12 3730
67 22. Selective production of difluoromethyl methyl ether from chlorodifluoromethane using alkali metal carbonates - J. Fluorine Chem. 2001, 107, 133 imagefile aziridine 2010-05-12 4618
66 23. Synthesis of Quaternary Ammoniocephalosporin Having Two Vinyl Groups Using Radical Promoted Thermal Isomerization - Bull. Kor. Chem. Soc. 2001, 22, 659 imagefile aziridine 2010-05-12 3819
65 24. New synthesis and ring opening of cis-3-alkylaziridine-2-carboxylates - Tetrahedron 2001, 57, 9655 imagefile aziridine 2010-05-12 4396
64 25. Asymmetric synthesis of β-amino-α-hydroxy acids through Lewis acid-mediated addition of ketone acetal to imines - Bull. Chem. Soc. Jpn. 2001, 74, 1667 imagefile aziridine 2010-05-12 4401
63 26. New Uses of Amino Acids as Chiral Building Blocks in Organic Synthesis - Org. Lett. 2001, 3, 3119 imagefile aziridine 2010-05-12 3767
62 27. Synthesis of Substituted-(l)-Tryptophanols from an Enantiomerically Pure Aziridine-2-methanol - Org. Lett. 2001, 3, 4197. imagefile aziridine 2010-05-12 3818
61 28. Synthesis and SAR of Aziridinylquinoline-5,8-diones as Agents against Malignant Tumor Cells - Bull. Kor. Chem. Soc. 2001, 22, 1067 imagefile aziridine 2010-05-12 3675
60 29. Syntheses of 1b -Methylcarbapenems Bearing 5-Methyl-4-hydroxypyrrolidinone - Chem. Pharm. Bull. 2002, 50, 415 imagefile aziridine 2010-05-12 3475
59 30. An Efficient Synthesis of N-Boc-D-Diphenylalanine from A Chiral Aziridine-2-Carboxylate - Heterocycles 2002, 57, 1143 imagefile aziridine 2010-05-12 3701


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