Sorafenib

EGFR Inhibitor

DB00398

Approved Indication

Sorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma.

10 Targets

4 Resistance Mutations

18 References

1UWH Structure Loaded

3D Structure PDB: 1UWH

Switch structure: RCSB ↗

Protein Targets

BRAF P15056 ✓ 3 PDB FGFR1 P11362 ✓ FLT1 P17948 ✓ FLT3 P36888 ✓ FLT4 P35916 ✓ KDR P35968 ✓ 2 PDB KIT P10721 ✓ PDGFRB P09619 ✓ RAF1 P04049 ✓ RET P07949 ✓

Mechanism of Action

Sorafenib interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in angiogenesis, thus sorafenib reduces blood flow to the tumor. Sorafenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.

Resistance Mutations — 12 resistance samples observed in COSMIC

Click a chip to highlight in viewer

FLT3

p.D835H 5 p.D835X 3 p.D835Y 5 p.F691L 5

Resistance mutations sourced from COSMIC Drug Resistance database. Cyan = on-target · Amber = off-target · numbered badge = PubMed references for that mutation

Details

DrugBank ID DB00398 ↗

Approval Date 2005-12-20

Molecular Weight 464.825 g/mol

Drug Class EGFR Inhibitor

ATC Codes L01XE05

Synonyms Sorafenibum

PubChem CID: 216239 ↗

ChEMBL CHEMBL1336 ↗

SMILES

CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

ADMET Profile

Computing properties…