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Sorafenib
•
Developed as a selective ATP-competitive RAF inhibitor
•
Inhibits CRAF (RAF-1) and BRAF , including BRAF
v600E
at
low nanomolar concentrations
•
Also targets VEGF2/3, PDGFR, FGFR-1, FLT3 and c-KIT
•
Preclinical data suggest good CNS bioavailability (10%
of systemic exposure)
•
Most advanced RAF inhibitor in clinical space
•
FDA approved for treatment of renal cell carcinoma and
hepatocellular carcinoma
•
Pediatric MTD determined and safety data established
in Phase I trials