TY - JOUR
T1 - Development of a sphingosine kinase 1 specific small-molecule inhibitor
AU - Hengst, Jeremy
AU - Wang, Xujun
AU - Sk, Ugir H.
AU - Sharma, Arun
AU - Amin, Shantu
AU - Yun, Jong
N1 - Funding Information:
This research was supported by the Jake Gittlen Cancer Research Institute and by a grant from Susan G. Komen for the Cure.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/12/15
Y1 - 2010/12/15
N2 - The sphingolipid metabolic pathway represents a potential source of new therapeutic targets for numerous hyperproliferative/inflammatory diseases. Targets such as the sphingosine kinases (SphKs) have been extensively studied and numerous strategies have been employed to develop inhibitors against these enzymes. Herein, we report on the optimization of our novel small-molecule inhibitor SKI-I (N′-[(2-hydroxy-1-naphthyl)methylene]-3-(2-naphthyl)-1H- pyrazole-5-carbohydrazide) and the identification of a SphK1-specific analog, SKI-178, that is active in vitro and in vivo. This SphK1 specific small-molecule, non-lipid like, inhibitor will be of use to elucidate the roles of SphK1 and SphK2 in the development/progression of hyperproliferative and/or inflammatory diseases.
AB - The sphingolipid metabolic pathway represents a potential source of new therapeutic targets for numerous hyperproliferative/inflammatory diseases. Targets such as the sphingosine kinases (SphKs) have been extensively studied and numerous strategies have been employed to develop inhibitors against these enzymes. Herein, we report on the optimization of our novel small-molecule inhibitor SKI-I (N′-[(2-hydroxy-1-naphthyl)methylene]-3-(2-naphthyl)-1H- pyrazole-5-carbohydrazide) and the identification of a SphK1-specific analog, SKI-178, that is active in vitro and in vivo. This SphK1 specific small-molecule, non-lipid like, inhibitor will be of use to elucidate the roles of SphK1 and SphK2 in the development/progression of hyperproliferative and/or inflammatory diseases.
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U2 - 10.1016/j.bmcl.2010.10.005
DO - 10.1016/j.bmcl.2010.10.005
M3 - Article
C2 - 21050755
AN - SCOPUS:78449295649
SN - 0960-894X
VL - 20
SP - 7498
EP - 7502
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 24
ER -