regorafenib

Ligand id: 5891

Name: regorafenib

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Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 92.35
Molecular weight 482.08
XLogP 5.09
No. Lipinski's rules broken 1

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
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
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
Absorption/Distribution
Regorafenib circulates in the enterohepatic system and is almost completely bound to plasma proteins (99.5%).
Biotransformation/Metabolism
CYP3A4 and UGT1A9 generate the metabolites of regorafenib, M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl) which have similar in vitro pharmacological activities and steady-state concentrations as regorafenib.
Elimination
In vivo excretion of radiolabelled regorafinib indicates that after 12 days a total of 90% was eliminated (71% in feces and 19% in urine).
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