Discovery of novel sphingosine kinase 1 inhibitors.
Sphingosine kinase 1 (SK1) is an important enzyme that regulates the balance between ceramide and sphingosine-1-phosphate (S1P). Potent and novel SK1 inhibitors (6ag, 9ab and 12aa) have been discovered through a series of modifications of sphingosine (1), the substrate of this enzyme.
Drug and Biomaterial R&D, Genzyme Corporation, 153 Second Avenue, Waltham, MA 02451, USA. yibin.xiang@genzyme.com
Yibin
Y
Xiang
Gary
G
Asmussen
Michael
M
Booker
Bradford
B
Hirth
John L
JL
Kane
Junkai
J
Liao
Kevin D
KD
Noson
Christopher
C
Yee
D000613:Aminobutyrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000099157:Sphingosine Kinase
D000613:Aminobutyrates; D004791:Enzyme Inhibitors; D006714:Homoserine; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D011392:Proline; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate