Structural Insights into Pharmacologic Targeting of the RAS/ RAF/MEK/ERK Pathway
Time: 4:15 pm
day: Day One
Details:
- Cryo-EM structures show how BRAF, MEK, and a 14-3-3 dimer or organized in autoinhibited and active states
- Binding of ATP in the active site of RAF is crucial for maintaining auto inhibition, RAF inhibitors that displace it cause activation
- RAS can engage autoinhibited RAF complexes without disrupting them
- Stabilizing autoinhibited RAF
- Complexes may be an attractive therapeutic alternative to blocking binding of active Ras or inhibiting active Raf
