Kinetics of the ceramide kinase inhibitor K1, a suppressor of mast-cell activation.
In a previous study, we synthesized a novel inhibitor of ceramide kinase, K1. In this study, we determined that inhibition by K1 is non-competitive and that four intact six-membered rings are important to the inhibitory activity. Furthermore, we identified an effective in vivo concentration for K1, at which it did not influence any cellular lipid synthesis other than that of ceramide 1-phosphate (C1P) using RBL-2H3 cells, and found that K1 suppressed the activation of mast cells.
Kumada
Hirotaka
H
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Science and Faculty of Advanced Life Sciences, Hokkaido University, Japan.
Mitsutake
Susumu
S
Inagaki
Yuichi
Y
Mitsunaga
Shino
S
Tsuchikawa
Hiroshi
H
Katsumura
Shigeo
S
Igarashi
Yasuyuki
Y
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D002250:Carbon Radioisotopes; D007476:Ionophores; D047428:Protein Kinase Inhibitors; D000001:Calcimycin; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase