regorafenib   Click here for help

GtoPdb Ligand ID: 5891

Synonyms: BAY 73-4506 | Stivarga®
Approved drug
regorafenib is an approved drug (FDA (2012), EMA (2013))
Compound class: Synthetic organic
Comment: Regorafenib is an inhibitor of multiple membrane-bound and intracellular kinases. Although the drug is approved it must carry a Boxed Warning alerting patients and clinicians that severe and fatal liver toxicity was observed in some patients in regorafenib clinical studies. Regorafenib is a Type-2 kinase inhibitor.
Click here for help
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: regorafenib

2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 92.35
Molecular weight 482.08
XLogP 3.91
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES CNC(=O)c1nccc(c1)Oc1ccc(c(c1)F)NC(=O)Nc1ccc(c(c1)C(F)(F)F)Cl
Isomeric SMILES CNC(=O)c1nccc(c1)Oc1ccc(c(c1)F)NC(=O)Nc1ccc(c(c1)C(F)(F)F)Cl
InChI InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
No information available.
Summary of Clinical Use Click here for help
Regorafenib is used to treat metastatic colorectal cancer and advanced gastrointestinal stromal tumours. In April 2017 the US FDA expanded approval to include treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Regorafenib is an orally-administered inhibitor of multiple kinases involved in various signaling pathways involved in tumor growth, including pathological processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. Inhibition of VEGFR2 and TIE2 may account for the drug's anti-angiogenic properties.
Pharmacokinetics Click here for help
Regorafenib circulates in the enterohepatic system and is almost completely bound to plasma proteins (99.5%).
CYP3A4 and UGT1A9 generate the metabolites of regorafenib, M-2 (N-oxide; BAY 75-7495) and M-5 (N-oxide and N-desmethyl; BAY 81-8752) which have similar in vitro pharmacological activities and steady-state concentrations as regorafenib [1].
In vivo excretion of radiolabelled regorafinib indicates that after 12 days a total of 90% was eliminated (71% in feces and 19% in urine).
External links Click here for help