van Leeuwen, Ingeborg M. M. published the artcileMechanism-specific signatures for small-molecule p53 activators, COA of Formula: C25H34N4O2S, the publication is Cell Cycle (2011), 10(10), 1590-1598, database is CAplus and MEDLINE.
Recent advances in the field of pharmacol. activation of the p53 tumor suppressor are beginning to be translated into the clinic. In addition, small mols. that activate p53 through established mechanisms of action are proving invaluable tools for basic research. Here we analyze and compare the effects of nutlin-3, tenovin-6 and low doses of actinomycin-D on p53 and its main neg. regulator, mdm2. We reveal striking differences in the speed at which these compounds increase p53 protein levels, with nutlin-3 having a substantial impact within minutes. We also show that nutlin-3 is very effective at increasing the synthesis of mdm2 mRNA, mdm2 being not only a modulator of p53 but also a transcriptional target. In addition, we show that nutlin-3 stabilizes mdm2’s conformation and protects mdm2 from degradation These strong effects of nutlin-3 on mdm2 correlate with a remarkable rate of recovery of p53 levels upon removal of the compound We discuss the potential application of our results as mol. signatures to assess the on-target effects of small-mol. mdm2 inhibitors. To conclude, we discuss the implications of our observations for using small-mol. p53 activators to reduce the growth of tumors retaining wild-type p53 or to protect normal tissues against the undesired side effects of conventional chemotherapy.
Cell Cycle published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H47NO8, COA of Formula: C25H34N4O2S.
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