Targeting the Protein-Protein Interaction Between the CDC37 Co-Chaperone and Client Kinases by an Allosteric RAF Dimer Breaker.

Braftide, originally designed as a potent allosteric RAF kinase dimer disruptor, was intended to inhibit RAF dimerization by targeting the conserved RAF dimer interface. Intriguingly, Braftide has also been observed to trigger proteasome-mediated protein degradation with an unclear mechanism of action. This study elucidates the mechanism underlying Braftide's dual functionality and assesses its potential as a chemical probe to target kinase-chaperone interaction.