Development of a High-throughput NanoBRET Screening Platform to Identify Modulators of the RAS/RAF Interaction.

ABSTRACT: Activating mutations in RAS are found in approximately 30% of human cancers, resulting in the delivery of a persistent signal to critical downstream effectors that drive tumorigenesis. RAS-driven malignancies respond poorly to conventional cancer treatments and inhibitors that target RAS directly are limited; therefore, the identification of new strategies and/or drugs to disrupt RAS signaling in tumor cells remains a pressing therapeutic need. Taking advantage of the live-cell bioluminescence resonance energy transfer (BRET) methodology, we describe the development of a NanoBRET screening platform to identify compounds that modulate binding between activated KRAS and the CRAF kinase, an essential effector of RAS that initiates ERK cascade signaling. Using this strategy, libraries c

SUBMITTER: Durrant DE 

PROVIDER: S-EPMC8419108 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature