Reversible Switch-2 Pocket Engagement Across KRAS Hotspot Mutants in Cells
Time: 10:15 am
day: Day One
- We have developed a novel live-cell target engagement assay for the formerly undruggable RAS using the NanoBRET target engagement approach
- The assay is capable of observing inhibitors of multiple mechanisms and can be utilized in a screening environment to detect weak affinity fragments with micromolar affinity
- We have found that KRAS and various KRAS hotspot mutants are vulnerable to reversible engagement in the switch-2 pocket.
- We will report on the selectivity profiles of recently reported reversible KRAS ligands including the KRAS(G12D) inhibitor MRTX1133