αC-Helix–Proximal Allostery as a Platform for Selective Kinase Modulation & Complex Degradation
- Introduce a scalable structure-guided platform that combines SuFEx-based high-throughput medicinal chemistry and direct-to-biology screening to systematically discover aC-helix–proximal allosteric pockets across kinases
- Show how aC-helix–proximal engagement yields signaling-state-selective BRAF inhibitors that preferentially target RAF dimers and suppress dimerdependent MAPK signaling
- Demonstrate that the same strategy can generate CDK8/CDK19 modulators that destabilize CDK8/CDK19–Cyclin C complexes and trigger proteasomedependent degradation without requiring bifunctional degrader architectures