Ligand id: 5713

Name: sunitinib

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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 8
Topological polar surface area 77.23
Molecular weight 398.21
XLogP 3.4
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumours.
Marketed formulations contain sunitinib malate (PubChem CID 6456015).
Mechanism Of Action and Pharmacodynamic Effects
Sunitinib inhibits multiple receptor tyrosine kinases, some of which are implicated in tumour growth, pathologic angiogenesis, and metastatic progression of cancer. Biochemical and cellular assays (including proliferation assays) have identified sunitinib, and its primary metabolite (desethyl sunitinib, PubChem CID 10292573), as inhibitors of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT) [6], Fms-like tyrosine kinase-3 (FLT3) [4], colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET).
Peak plasma concentrations of sunitinib are reached between 6 and 12 hours following oral administration. Food has no effect on the bioavailability of sunitinib. Binding of sunitinib and its primary metabolite (desethyl sunitinib) to human plasma protein in vitro was 95% and 90%, respectively.
Sunitinib is metabolized primarily by CYP3A4 in the liver, which produces its primary active metabolite, desethyl sunitinib, which is then further metabolized by the same isoenzyme.
Elimination in the feces (61%) and urine (16%)
Population pharmacokinetics
Pharmacokinetics of nilotinib are not significantly affected by age, body weight, race, or gender. There are no clinically relevant effects observed in the eldery population. Effects in children have not been evaluated.
Organ function impairment
Systemic exposure to sunitinib is similar in subjects with severe renal impairment compared with subjects with healthy renal function, but is 47% lower in subjects undergoing hemodialysis due to end stage renal disease (ESRD). Systemic exposures after a single dose of sunitinib are similar in subjects with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment compared with subjects with healthy hepatic function. Sunitinib has not been studied in patients with severe (Child-Pugh class C) hepatic impairment.
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