Barbituric acid derivative BAS 02104951 inhibits PKC, PKC, PKC/RACK2 interaction, Elk-1 phosphorylation in HeLa and PKC and translocation in PC3 cells following TPA-induction
Source: The Journal of Biochemistry, Volume 149, Number 3, 10 March 2011 , pp. 331-336(6)
Publisher: Oxford University Press
Abstract:Protein kinase C (PKC) is a family of at least 10 isozymes involved in the activation of different signal transduction pathways. The exact function of these isozymes is not known at present. Isozyme-selective inhibitors would be important to explain the function of the different PKCs and are anticipated to have pharmaceutical potential. Here we report that the small organic molecule BAS 02104951 [5-(1,3-benzodioxol-5-ylmethylene)-1-(phenylmethyl)-2,4,6(1H,3H,5H)-pyrimidinetrion], a barbituric acid derivative, inhibited PKC and PKC in vitro (IC50 18 and 36 M, respectively). BAS 02104951 also inhibited the interaction of PKC with its adaptor protein receptor for activated C-kinase 2 (RACK2) (IC50 28.5 M). BAS 02104951 also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Elk-1 phosphorylation in HeLa cells, translocation of PKC and PKC to the membrane following treatment of PC3 cells with TPA. The compound did not inhibit the proliferation of PC3 and HeLa cells. BAS 02104951 can be used as selective inhibitor of PKC in cells not expressing PKC and may serve as a basis for the rational development of a selective inhibitor of PKC or PKC, or for an inhibitor of the PKC/RACK2 interaction.
Document Type: Regular paper
Publication date: 2011-03-10