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=CC=C(F)C=C23)=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

Molecular Formula	C22H27FN4O2
Molecular Weight	398.4738
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

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 33 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	0.79 nM [Kd]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25882519	Inhibitor 8504	83.1 nM [IC50]
Vascular endothelial growth factor receptor 1 44 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22765894	Inhibitor 8504	1.0 nM [IC50]
Vascular endothelial growth factor receptor 2 112 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23583911	Inhibitor 8504	18.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	50.0 nM [Kd]
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22221201	Inhibitor 8504	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 8583	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 8583	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 8583	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
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
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
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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
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
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

T_1/2

Value	Dose	Analyte	Population
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
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
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
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
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% 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 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F 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 Health Status: unhealthy Age Group: 74 years Sex: M 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 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 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 Health Status: unhealthy 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 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Fever	1 patient Disc. AE	50 mg 1 times / day steady, oral 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Nausea	1 patient Disc. AE	50 mg 1 times / day steady, oral 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Thrombocytopenia	1 patient Disc. AE	50 mg 1 times / day steady, oral 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Vomiting	1 patient Disc. AE	50 mg 1 times / day steady, oral 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 Health Status: unhealthy Age Group: 52-77 years Sex: M+F 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 Health Status: unhealthy Age Group: 74 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25757921
Liver failure	2 patients Disc. AE	50 mg 1 times / day steady, oral 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 Health Status: unhealthy 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 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 Health Status: unhealthy 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 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 Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 CYP4A9/11 35 P-gp 1741	CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 CYP2E1 729 P-gp 2052 BCRP 697	CYP1A2 832 CYP2E1 131

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [IC50 39 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 110 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 140 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 24 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 28 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 5.4 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki 54 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	yes [Ki >150 uM]
CYP4A9/11 35	inhibitor 4027 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 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	minor
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	moderate
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021938_S000_Sutent_BioPharmR.pdf	no
CYP3A4 1946	substrate 4014 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 2263	inhibitor 2237 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
eMolecules	23296409	https://www.emolecules.com/cgi-bin/more?vid=23296409
eMolecules	27524016	https://www.emolecules.com/cgi-bin/more?vid=27524016
MolPort	MolPort-006-167-758	https://www.molport.com/shop/molecule-link/MolPort-006-167-758
ZINC	ZINC000003964325	http://zinc15.docking.org/substances/ZINC000003964325

PubMed

Title	Date	PubMed
Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.	2016-01-22	26581635
Identification of a Mitochondrial DNA Polymerase Affecting Cardiotoxicity of Sunitinib Using a Genome-Wide Screening on S. pombe Deletion Library.	2016-01	26385865
Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma.	2015-12	26387812
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.	2015-11	26259608
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.	2015-06	25752796
Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries.	2014-06-25	24751611
Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway.	2014-03	24247421
Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs.	2014-01-15	24321339
A high-throughput screen for teratogens using human pluripotent stem cells.	2014-01	24154490
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.	2013-12	24052561
Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes.	2013-10-01	23707608
Sunitinib, a tyrosine kinase inhibitor, induces cytochrome P450 1A1 gene in human breast cancer MCF7 cells through ligand-independent aryl hydrocarbon receptor activation.	2013-05	23288144
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013-04-15	23398362
Activity-based kinase profiling of approved tyrosine kinase inhibitors.	2013-02	23279183
A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-κB signaling in chordoma biology.	2013	24223206
Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model.	2012-08	22374800
HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis.	2012-07-01	22269210
Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells.	2012-07	22532600
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.	2012-05	22343322
Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.	2011-11-15	21906609
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011-10-30	22037377
Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.	2011-06	21482694
Sunitinib improves chemotherapeutic efficacy and ameliorates cisplatin-induced nephrotoxicity in experimental animals.	2011-05	20652569
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
Autophagy plays an important role in sunitinib-mediated cell death in H9c2 cardiac muscle cells.	2010-10-01	20637791
Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?	2010-08-12	20698227
Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity.	2010-08	20616376
Synthesis and structure-activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors.	2010-07-01	20570526
The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity.	2010-04-15	20045709
Sequential sorafenib and sunitinib for renal cell carcinoma.	2009-07	19447417
Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2.	2009-06-28	19232821
Novel agents for renal cell carcinoma require novel selection paradigms to optimise first-line therapy.	2009-05	19232474
Fatal liver failure in a patient on acetaminophen treated with sunitinib malate and levothyroxine.	2009-04	19336648
Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma.	2008-08-01	18669461
Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.	2007-01-11	17215529
Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial.	2006-10-14	17046465
Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour.	2006-07	16772838
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.	2003-01	12538485

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

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:28:36 GMT 2025` Edited by `admin` on `Mon Mar 31 18:28:36 GMT 2025`
Record UNII	V99T50803M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SU-11248

Preferred Name

English

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

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