Rottlerin, a novel protein kinase inhibitor.
Rottlerin, a compound from Mallotus philippinensis, is shown to inhibit protein kinases with some specificity for PKC. To some extent, the novel inhibitor is able to differentiate between PKC isoenzymes, with IC50 values for PKC delta of 3-6 microM, PKC alpha,beta,gamma of 30-42 microM and PKC epsilon,eta,zeta of 80-100 microM. Inhibition of PKC appears, at least in part, to be due to a competition between rottlerin and ATP. Among the protein kinases tested, only CaM-kinase III is suppressed by rottlerin as effectively as PKC delta. The chemical structure of rottlerin might serve as a basis for the development of novel inhibitors with improved selectivity for a distinct PKC isoenzyme, such as PKC delta, or for CaM-kinase III.
Gschwendt
M
M
German Cancer Research Center, Heidelberg.
Müller
H J
HJ
Kielbassa
K
K
Zang
R
R
Kittstein
W
W
Rincke
G
G
Marks
F
F
D000098:Acetophenones / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001667:Binding, Competitive; D003402:Creatine Kinase / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D013552:Swine
D000098:Acetophenones; D001578:Benzopyrans; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; C085746:rottlerin; D015688:Oncogene Protein pp60(v-src); D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D003402:Creatine Kinase