Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/190110
Peptidomimetics designed to bind to RAS effector domain are promising cancer therapeutic compounds.
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Oncogenic RAS proteins are important for driving tumour formation, and for maintenance of the transformed phenotype, and thus their relevance as a cancer therapeutic target is undeniable. We focused here on obtaining peptidomimetics, which have good pharmacological properties, to block Ras-effector interaction. Computational analysis was used to identify hot spots of RAS relevant for these interactions and to screen a library of peptidomimetics. Nine compounds were synthesized and assayed for their activity as RAS inhibitors in cultured cells. Most of them induced a reduction in ERK and AKT activation by EGF, a marker of RAS activity. The most potent inhibitor disrupted Raf and PI3K interaction with oncogenic KRAS, corroborating its mechanism of action as an inhibitor of protein-protein interactions, and thus validating our computational methodology. Most interestingly, improvement of one of the compounds allowed us to obtain a peptidomimetic that decreased the survival of pancreatic cancer cell lines harbouring oncogenic KRAS
Matèries
Matèries (anglès)
Citació
Citació
PALLARA, Chiara, CABOT, Débora, RIVAS, Josep, BRUN, Sonia, SECO, Jesús, ABUASAKER, Baraa, TARRAGÓ CLUA, Maria teresa, JAUMOT I PIJOAN, Montserrat, PRADES, Roger, AGELL I JANÉ, Neus. Peptidomimetics designed to bind to RAS effector domain are promising cancer therapeutic compounds.. _Scientific Reports_. 2022. Vol. 22, núm. 12, pàgs. 15810. [consulta: 21 de gener de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/190110]