Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum.
Meridianins are brominated 3-(2-aminopyrimidine)-indoles which are purified from Aplidium meridianum, an Ascidian from the South Atlantic (South Georgia Islands). We here show that meridianins inhibit various protein kinases such as cyclin-dependent kinases, glycogen synthase kinase-3, cyclic nucleotide-dependent kinases and casein kinase 1. Meridianins prevent cell proliferation and induce apoptosis, a demonstration of their ability to enter cells and to interfere with the activity of kinases important for cell division and cell death. These results suggest that meridianins constitute a promising scaffold from which more potent and selective protein kinase inhibitors could be designed.
Gompel
Marie
M
C.N.R.S., Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France.
Leost
Maryse
M
De Kier Joffe
Elisa Bal
EB
Puricelli
Lydia
L
Franco
Laura Hernandez
LH
Palermo
Jorge
J
Meijer
Laurent
L
D000631:Aminopyridines / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D026121:Indole Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D047428:Protein Kinase Inhibitors; D014561:Urochordata / Q000201:enzymology*
D000631:Aminopyridines; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors