sunitinib   Click here for help

GtoPdb Ligand ID: 5713

Synonyms: SU11248 | Sutent®
Approved drug PDB Ligand
sunitinib is an approved drug (FDA and EMA (2006))
Compound class: Synthetic organic
Comment: Sunitinib is a Type-1 kinase inhibitor and was first approved by the US FDA and EMA in 2006.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: sunitinib

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 77.23
Molecular weight 398.21
XLogP 2.94
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCN(CCNC(=O)c1c(C)[nH]c(c1C)C=C1C(=O)Nc2c1cc(F)cc2)CC
Isomeric SMILES CCN(CCNC(=O)c1c(C)[nH]c(c1C)/C=C/1\C(=O)Nc2c1cc(F)cc2)CC
InChI InChI=1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
InChI Key WINHZLLDWRZWRT-ATVHPVEESA-N
No information available.
Summary of Clinical Use Click here for help
Approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumours.
Marketed formulations contain sunitinib malate (PubChem CID 6456015). In November 2017, the FDA expanded approval to include treatment of adult patients at high risk of recurrent renal cell carcinoma following nephrectomy, based on positive outcomes from clinical trial NCT00375674.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
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).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00375674 A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer Phase 3 Interventional Pfizer
Pharmacokinetics Click here for help
Absorption/Distribution
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.
Biotransformation/Metabolism
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
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.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)