Sunitinib

Sunitinib

Clinical data
Trade names	Sutent
AHFS/Drugs.com	Monograph
MedlinePlus	a607052
License data	EU EMA: Sutent US FDA: Sunitinib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE04 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	Unaffected by food
Protein binding	95%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	40 to 60 hours (sunitinib) 80 to 110 hours (metabolite)
Excretion	Fecal (61%) and renal (16%)
Identifiers
IUPAC name N-(2-diethylaminoethyl)-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
CAS Number	341031-54-7 N
PubChem (CID)	5329102
IUPHAR/BPS	5713
DrugBank	DB01268 Y
ChemSpider	4486264 Y
UNII	V99T50803M Y
KEGG	D06402 Y
ChEBI	CHEBI:38940 Y
ChEMBL	CHEMBL535 Y
Chemical and physical data
Formula	C22H27FN4O2
Molar mass	398.474 g/mol 532.561 g/mol (malate)
3D model (Jmol)	Interactive image
SMILES CCN(CC)CCNC(=O)c1c(c([nH]c1C)/C=C\2/c3cc(ccc3NC2=O)F)C
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- Y Key:WINHZLLDWRZWRT-ATVHPVEESA-N Y
NY (what is this?)

Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs).

These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these targets therefore reduces tumor vascularization and triggers cancer cell apoptosis and thus results in tumor shrinkage.

Sunitinib also inhibits CD117 (c-KIT), the receptor tyrosine kinase that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors. It has been recommended as a second-line therapy for patients whose tumors develop mutations in c-KIT that make them resistant to imatinib, or who the cannot tolerate the drug.

In addition, sunitinib binds other receptors. These include:

The fact that sunitinib targets many different receptors, leads to many of its side effects such as the classic hand-foot syndrome, stomatitis, and other dermatologic toxicities.