<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Gomes, Ana Sara</style></author><author><style face="normal" font="default" size="100%">Ramos, Helena</style></author><author><style face="normal" font="default" size="100%">Gomes, Sara</style></author><author><style face="normal" font="default" size="100%">Loureiro, Joana B.</style></author><author><style face="normal" font="default" size="100%">Soares, Joana</style></author><author><style face="normal" font="default" size="100%">Barcherini, Valentina</style></author><author><style face="normal" font="default" size="100%">Monti, Paola</style></author><author><style face="normal" font="default" size="100%">Fronza, Gilberto</style></author><author><style face="normal" font="default" size="100%">Oliveira, Carla</style></author><author><style face="normal" font="default" size="100%">Domingues, Lucília</style></author><author><style face="normal" font="default" size="100%">Bastos, Margarida</style></author><author><style face="normal" font="default" size="100%">Dourado, Daniel F.A.R.</style></author><author><style face="normal" font="default" size="100%">Carvalho, Ana Luísa</style></author><author><style face="normal" font="default" size="100%">Romão, Maria João</style></author><author><style face="normal" font="default" size="100%">Pinheiro, Benedita</style></author><author><style face="normal" font="default" size="100%">Marcelo, Filipa</style></author><author><style face="normal" font="default" size="100%">Carvalho, Alexandra</style></author><author><style face="normal" font="default" size="100%">Santos, Maria M.M.</style></author><author><style face="normal" font="default" size="100%">Saraiva, Lucília</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactivates multiple hotspot mutations</style></title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Cancer</style></keyword><keyword><style  face="normal" font="default" size="100%">Chemotherapy</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutant</style></keyword><keyword><style  face="normal" font="default" size="100%">p53</style></keyword><keyword><style  face="normal" font="default" size="100%">Reactivator</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.sciencedirect.com/science/article/pii/S0304416519302260</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">1864</style></volume><pages><style face="normal" font="default" size="100%">129440</style></pages><isbn><style face="normal" font="default" size="100%">0304-4165</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;BackgroundHalf of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with in vitro and in vivo p53-dependent antitumor activity. The present work aimed a mechanistic elucidation of mutp53 reactivation by SLMP53-1.&lt;br /&gt;
Methods and results&lt;br /&gt;
By cellular thermal shift assay (CETSA), it is shown that SLMP53-1 induces wt and mutp53 R280K thermal stabilization, which is indicative of intermolecular interactions with these proteins. Accordingly, in silico studies of wt and mutp53 R280K DNA-binding domain with SLMP53-1 unveiled that the compound binds at the interface of the p53 homodimer with the DNA minor groove. Additionally, using yeast and p53-null tumor cells ectopically expressing distinct highly prevalent mutp53, the ability of SLMP53-1 to reactivate multiple mutp53 is evidenced.&lt;br /&gt;
Conclusions&lt;br /&gt;
SLMP53-1 is a p53-activating agent with the ability to directly target wt and a set of hotspot mutp53.&lt;br /&gt;
General Significance&lt;br /&gt;
This work reinforces the encouraging application of SLMP53-1 in the personalized treatment of cancer patients harboring distinct p53 status.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><notes><style face="normal" font="default" size="100%">n/a</style></notes></record></records></xml>