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 30 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	0.79 nM [Kd]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25882519	Inhibitor 8297	83.1 nM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22765894	Inhibitor 8297	1.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23583911	Inhibitor 8297	18.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	50.0 nM [Kd]
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22221201	Inhibitor 8297	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 8429	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 2006
Advanced renal cell carcinoma 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf	Primary	Approved 8429	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 2006
Pancreatic neuroendocrine tumors 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021938s031lbl.pdf	Primary	Approved 8429	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 2006

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 1737 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 CYP4A9/11 37 P-gp 1461	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 P-gp 1537 BCRP 561	CYP1A2 701 CYP2E1 128

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [IC50 39 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 110 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 140 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 24 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 28 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 5.4 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 54 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP4A9/11 37	inhibitor 3277 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 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	moderate
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 1737	substrate 3367 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 1647	inhibitor 1626 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
Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2.	2009 Jun 28	19232821
Novel agents for renal cell carcinoma require novel selection paradigms to optimise first-line therapy.	2009 May	19232474
Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity.	2010 Aug	20616376
Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?	2010 May-Jun	20698227
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Autophagy plays an important role in sunitinib-mediated cell death in H9c2 cardiac muscle cells.	2010 Oct 1	20637791
Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.	2011 Jun	21482694
Sunitinib improves chemotherapeutic efficacy and ameliorates cisplatin-induced nephrotoxicity in experimental animals.	2011 May	20652569
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
Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells.	2012 Jul	22532600
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
A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-κB signaling in chordoma biology.	2013	24223206
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.	2013 Dec	24052561
Activity-based kinase profiling of approved tyrosine kinase inhibitors.	2013 Feb	23279183
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
Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes.	2013 Oct 1	23707608
A high-throughput screen for teratogens using human pluripotent stem cells.	2014 Jan	24154490
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
Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma.	2015 Dec	26387812
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.	2015 Jun	25752796
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
Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.	2016 Jan 22	26581635

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