Brain Tumours

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