Development of KRAS/ PDE6D molecular glues to inhibit KRAS by nucleo-cytoplasmic sequestration KU Leuven
KRAS is a high-priority drug target in cancer. Its obligate localization to the plasma membrane is aided by the trafficking chaperone PDE6D. We have previously shown that inhibition of PDE6D can block KRAS activity. However, current PDE6D inhibitors have unfavorable properties and lack KRAS selectivity due to their design. We recently published that stabilization of the KRAS/PDE6D complex can sequester KRAS to the cytoplasm via its specific ...