SUNITINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H27FN4O2
Molecular Weight	398.4738
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C

InChI

InChIKey=WINHZLLDWRZWRT-ATVHPVEESA-N

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-

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01268 | http://reference.medscape.com/drug/sutent-sunitinib-342201 | https://www.drugs.com/cdi/sunitinib.html | https://www.ncbi.nlm.nih.gov/pubmed/25272897 | https://www.ncbi.nlm.nih.gov/pubmed/28413468

Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor. Sunitinib was evaluated for its inhibitory activity against a variety of kinases and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib adverse events are considered somewhat manageable and the incidence of serious adverse events low. The most common adverse events associated with sunitinib therapy are fatigue, diarrhea, nausea, anorexia, hypertension, yellow skin discoloration, hand-foot skin reaction, and stomatitis. In the placebo-controlled Phase III GIST study, adverse events which occurred more often with sunitinib than placebo included diarrhea, anorexia, skin discoloration, mucositis/stomatitis, asthenia, altered taste, and constipation. Dose reductions were required in 50% of the patients studied in RCC in order to manage the significant toxicities of this agent.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Platelet-derived growth factor receptor alpha 29 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8146	0.79 nM [Kd]
Platelet-derived growth factor receptor beta 54 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25882519	Inhibitor 8146	83.1 nM [IC50]
Vascular endothelial growth factor receptor 1 39 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22765894	Inhibitor 8146	1.0 nM [IC50]
Vascular endothelial growth factor receptor 2 100 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23583911	Inhibitor 8146	18.0 nM [IC50]
Vascular endothelial growth factor receptor 3 39 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8146	50.0 nM [Kd]
Stem cell growth factor receptor 51 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22221201	Inhibitor 8146	8.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Gastrointestinal stromal tumor 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf	Primary	Approved 8307	SUTENT Approved Use SUTENT is a kinase inhibitor indicated for the treatment of: Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. (1.1) Advanced renal cell carcinoma (RCC). (1.2) Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. (1.3) 1.1 Gastrointestinal Stromal Tumor (GIST) SUTENT is indicated for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. 1.2 Advanced Renal Cell Carcinoma (RCC) SUTENT is indicated for the treatment of advanced renal cell carcinoma. 1.3 Advanced Pancreatic Neuroendocrine Tumors (pNET) SUTENT is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Launch Date 1.13823357E12
Advanced renal cell carcinoma 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf	Primary	Approved 8307	SUTENT Approved Use SUTENT is a kinase inhibitor indicated for the treatment of: Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. (1.1) Advanced renal cell carcinoma (RCC). (1.2) Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. (1.3) 1.1 Gastrointestinal Stromal Tumor (GIST) SUTENT is indicated for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. 1.2 Advanced Renal Cell Carcinoma (RCC) SUTENT is indicated for the treatment of advanced renal cell carcinoma. 1.3 Advanced Pancreatic Neuroendocrine Tumors (pNET) SUTENT is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Launch Date 1.13823357E12
Pancreatic neuroendocrine tumors 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf	Primary	Approved 8307	SUTENT Approved Use SUTENT is a kinase inhibitor indicated for the treatment of: Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. (1.1) Advanced renal cell carcinoma (RCC). (1.2) Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. (1.3) 1.1 Gastrointestinal Stromal Tumor (GIST) SUTENT is indicated for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. 1.2 Advanced Renal Cell Carcinoma (RCC) SUTENT is indicated for the treatment of advanced renal cell carcinoma. 1.3 Advanced Pancreatic Neuroendocrine Tumors (pNET) SUTENT is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Launch Date 1.13823357E12

C_max

Value	Dose	Co-administered	Analyte	Population
4.35 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		N-DESETHYL SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
51.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22743295	37.5 mg 1 times / day steady-state, oral dose: 37.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ERLOTINIB	ERLOTINIB	SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
21.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22179104	15 mg/m² 1 times / day steady-state, oral dose: 15 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
559 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		N-DESETHYL SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1056 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22743295	37.5 mg 1 times / day steady-state, oral dose: 37.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ERLOTINIB	ERLOTINIB	SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1369 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
791 ng × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22179104	15 mg/m² 1 times / day steady-state, oral dose: 15 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
111 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	N-DESETHYL SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
63.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
22.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22179104	15 mg/m² 1 times / day steady-state, oral dose: 15 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:	SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
10% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	N-DESETHYL SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20049443	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SUNITINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021938s13s17s18lbl.pdf		SUNITINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	Disc. AE: Thrombocytopenia, Fever... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1 patient) Fever (1 patient) Fatigue (1 patient) Nausea (1 patient) Vomiting (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
25 mg 1 times / day steady, oral Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 74 years n = 1 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	Disc. AE: Fever... AEs leading to discontinuation/dose reduction: Fever (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
350 mg 1 times / day steady, oral Highest studied dose Dose: 350 mg, 1 times / day Route: oral Route: steady Dose: 350 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf / https://pubmed.ncbi.nlm.nih.gov/14654525	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf / https://pubmed.ncbi.nlm.nih.gov/14654525	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf / https://pubmed.ncbi.nlm.nih.gov/14654525
175 mg steady, oral Studied dose Dose: 175 mg Route: oral Route: steady Dose: 175 mg Sources: https://cancerres.aacrjournals.org/content/66/8_Supplement/684.2	unhealthy Health Status: unhealthy Condition: advanced solid tumors Sources: https://cancerres.aacrjournals.org/content/66/8_Supplement/684.2	Sources: https://cancerres.aacrjournals.org/content/66/8_Supplement/684.2
50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf	unhealthy n = 202 Health Status: unhealthy Population Size: 202 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf	Disc. AE: Anemia, Liver failure... AEs leading to discontinuation/dose reduction: Anemia (4 patients) Liver failure (2 patients) Metabolic disorder (3 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf

AEs

AE	Significance	Dose	Population
Fatigue	1 patient Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Fever	1 patient Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Nausea	1 patient Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Thrombocytopenia	1 patient Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Vomiting	1 patient Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 52-77 years n = 5 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 52-77 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Fever	1 patient Disc. AE	25 mg 1 times / day steady, oral Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25757921	unhealthy, 74 years n = 1 Health Status: unhealthy Condition: Renal Cell Carcinoma Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Liver failure	2 patients Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf	unhealthy n = 202 Health Status: unhealthy Population Size: 202 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf
Metabolic disorder	3 patients Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf	unhealthy n = 202 Health Status: unhealthy Population Size: 202 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf
Anemia	4 patients Disc. AE	50 mg 1 times / day steady, oral (starting) Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf	unhealthy n = 202 Health Status: unhealthy Population Size: 202 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inducer 753	substrate 985 inhibitor 1695	substrate 1168 inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP2E1 846 CYP3A4/5 261 CYP4A9/11 34 P-gp 1401	CYP1A2 1013 CYP2A6 510 CYP2B6 648 CYP2C8 670 CYP2C19 955 CYP2E1 633 P-gp 1491 BCRP 545	CYP1A2 671 CYP2E1 121

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 929	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [IC50 39 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 110 uM]
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 140 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 24 uM]
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 28 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 5.4 uM]
CYP3A4/5 314	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 54 uM]
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP4A9/11 34	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2B6 648	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C8 670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C9 985	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	moderate
BCRP 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2A6 510	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 633	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes	yes (co-administration study) Comment: ketoconazole increased auc of sunitinib by 51% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_PharmR.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:38940	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:38940
ChemicalBook	CB9728174	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9728174
MolPort	MolPort-006-167-758	https://www.molport.com/shop/molecule-link/MolPort-006-167-758
ZINC	ZINC000003964325	http://zinc15.docking.org/substances/ZINC000003964325
eMolecules	23296409	https://www.emolecules.com/cgi-bin/more?vid=23296409
eMolecules	27524016	https://www.emolecules.com/cgi-bin/more?vid=27524016

PubMed

Title	Date	PubMed
In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship.	2003 Jan	12538485
Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour.	2006 Jul	16772838
Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial.	2006 Oct 14	17046465
Fatal liver failure in a patient on acetaminophen treated with sunitinib malate and levothyroxine.	2009 Apr	19336648
Sequential sorafenib and sunitinib for renal cell carcinoma.	2009 Jul	19447417
The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity.	2010 Apr 15	20045709
Synthesis and structure-activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors.	2010 Jul 1	20570526
Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?	2010 May-Jun	20698227
Autophagy plays an important role in sunitinib-mediated cell death in H9c2 cardiac muscle cells.	2010 Oct 1	20637791
Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.	2011 Nov 15	21906609
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model.	2012 Aug	22374800
HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis.	2012 Jul 1	22269210
Evaluation of subchronic toxicity of SIM010603, a potent inhibitor of receptor tyrosine kinase, after 28-day repeated oral administration in SD rats and beagle dogs.	2012 May	22343322
Sunitinib, a tyrosine kinase inhibitor, induces cytochrome P450 1A1 gene in human breast cancer MCF7 cells through ligand-independent aryl hydrocarbon receptor activation.	2013 May	23288144
Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs.	2014 Jan 15	24321339
Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries.	2014 Jun 25	24751611
Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway.	2014 Mar	24247421
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.	2015 Nov	26259608
Identification of a Mitochondrial DNA Polymerase Affecting Cardiotoxicity of Sunitinib Using a Genome-Wide Screening on S. pombe Deletion Library.	2016 Jan	26385865

Patents

Sample Use Guides

In Vivo Use Guide

GIST: 50 mg orally once daily, with or without food, 4 weeks on treatment followed by 2 weeks off. pNET: 37.5 mg orally once daily, with or without food, continuously without a scheduled off-treatment period

Route of Administration: Oral

In Vitro Use Guide

Cell viability assays following suni¬tinib treatment were performed using a cell counting kit 8 (CCK 8; Dojindo Molecular Technologies, Inc., Kumamoto, Japan). PC 3 and LNCaP cells were seeded in 96 well plates (1x104 cells/well) with culture medium supplemented with 10% FBS and were incubated at 37˚C in incubator with an atmosphere of 5% CO2 for 12 h to allow adherence. Cells were treated with 10 μl culture medium containing 0, 5, 10 or 20 μmol/l of sunitinib for 24 h. A total of 10 μl CCK 8 was added to the cells, following sunitinib treatment, and the cells were incubated for a further 2 h at 37˚C. A microplate reader was used to measure the absorbance of each well at 450 nm

Name

Type

Language

SUNITINIB

Official Name

English

SU-011248

Code

English

1H-PYRROLE-3-CARBOXAMIDE, N-(2-(DIETHYLAMINO)ETHYL)-5-((Z)-(5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-

Systematic Name

English

NSC-736511

Code

English

SU-11248

Code

English

SUNITINIB [VANDF]

Common Name

English

N-(2-(DIETHYLAMINO)ETHYL)-5-((Z)-(5-FLUORO-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE

Systematic Name

English

NSC-750690

Code

English

SU011248

Code

English

Sunitinib [WHO-DD]

Common Name

English

SUNITINIB [EMA EPAR]

Common Name

English

SUNITINIB [MI]

Common Name

English

sunitinib [INN]

Common Name

English

N-(2-(DIETHYLAMINO)ETHYL)-5-((Z)-(5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

L01XE04