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