8 documents found, page 1 of 1
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A.; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
A selective p53 activator and anticancer agent to improve colorectal cancer the...
Ramos, Helena; Soares, Maria I. L.; Silva, Joana; Raimundo, Liliana; Calheiros, Juliana; Gomes, Célia; Reis, Flávio; Monteiro, Filipe A.; Nunes, CláudiaImpairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring W...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mut...
SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promisin...
Gomes, Sara; Bosco, Bartolomeo; Loureiro, Joana B.; Ramos, Helena; Raimundo, Liliana; Soares, Joana; Nazareth, Nair; Barcherini, ValentinaHalf of human cancers harbor <i>TP53</i> mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds...
DIMP53-1: a novel small-molecule dual inhibitor of p53-MDM2/X interactions with...
Soares, Joana; Espadinha, Margarida; Raimundo, Liliana; Ramos, Helena; Gomes, Ana Sara; Gomes, Sara; Loureiro, Joana B.; Inga, Alberto; Reis, FlávioThe transcription factor p53 plays a crucial role in cancer development and dissemination, and thus, p53-targeted therapies are among the most encouraging anticancer strategies. In human cancers with wild-type (wt) p53, its inactivation by interaction with murine double minute (MDM)2 and MDMX is a common event. Simultaneous inhibition of the p53 interaction with both MDMs is crucial to restore the tumor suppres...
Reactivation of wild-type and mutant p53 by tryptophanolderived oxazoloisoindol...
Soares, Joana; Raimundo, Liliana; Pereira, Nuno A. L.; Monteiro, Ângelo; Gomes, Sara; Bessa, Cláudia; Pereira, Clara; Queiroz, Glória; Bisio, AlessandraRestoration of the p53 pathway, namely by reactivation of mutant (mut) p53, represents a valuable anticancer strategy. Herein, we report the identification of the enantiopure tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a novel reactivator of wild-type (wt) and mut p53, using a yeast-based screening strategy. SLMP53-1 has a p53-dependent anti-proliferative activity in human wt and mut p53R280K-expressi...
Discovery of a new small-molecule inhibitor of p53–MDM2 interaction using a yea...
Leão, Mariana; Pereira, Clara; Bisio, Alessandra; Ciribilli, Yari; Paiva, Ana M.; Machado, Neuza; Palmeira, Andreia; Fernandes, Miguel X.; Sousa, EmíliaThe virtual screening of a library of xanthone derivatives led us to the identification of potential novel MDM2 ligands. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast phenotypic assay, herein developed for the initial screening. Using this approach, in association with a yeast p53 transactivation assay, the pyranoxanthone (3,4-dihydro-12- hydroxy-2,2-dimeth...