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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H27FN4O2.C4H6O5
Molecular Weight 532.5612
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SUNITINIB MALATE

SMILES

O[C@@H](CC(O)=O)C(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=CC=C(F)C=C23)=C1C

InChI

InChIKey=LBWFXVZLPYTWQI-IPOVEDGCSA-N
InChI=1S/C22H27FN4O2.C4H6O5/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;5-2(4(8)9)1-3(6)7/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28);2,5H,1H2,(H,6,7)(H,8,9)/b17-12-;/t;2-/m.0/s1

HIDE SMILES / InChI

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

Molecular Formula C4H6O5
Molecular Weight 134.0874
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

PubMed

PubMed

TitleDatePubMed
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
Imatinib mesylate-induced acute hepatitis in a patient treated for gastrointestinal stromal tumour.
2006 Jul
Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial.
2006 Oct 14
Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
2007 Jan 11
Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma.
2008 Aug 1
Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?
2010 May-Jun
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Autophagy plays an important role in sunitinib-mediated cell death in H9c2 cardiac muscle cells.
2010 Oct 1
Sunitinib improves chemotherapeutic efficacy and ameliorates cisplatin-induced nephrotoxicity in experimental animals.
2011 May
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model.
2012 Aug
HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis.
2012 Jul 1
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
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.
2013 Dec
Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes.
2013 Oct 1
Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs.
2014 Jan 15
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
Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.
2016 Jan 22
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 Oct 21 20:36:34 UTC 2019
Edited
by admin
on Mon Oct 21 20:36:34 UTC 2019
Record UNII
LVX8N1UT73
Record Status Validated (UNII)
Record Version
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Name Type Language
SUNITINIB MALATE
JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
SUNITINIB MALATE [MART.]
Common Name English
SUNITINIB MALATE [ORANGE BOOK]
Common Name English
SUNITINIB MALATE [MI]
Common Name English
SUNITINIB L-MALATE
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 HYDROGEN (2S)-2-HYDROXYBUTANEDIOATE
Common Name English
SUNITINIB MALATE [WHO-DD]
Common Name English
BUTANEDIOIC ACID, 2-HYDROXY-, (2S)-, COMPD. WITH 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 (1:1)
Systematic Name English
SU010398
Code English
SUNITINIB MALATE [USAN]
Common Name English
PHA-290940AD
Code English
SUNITINIB MALATE [JAN]
Common Name English
SUTENT
Brand Name English
SU-010398
Code English
BUTANEDIOIC ACID, HYDROXY-, (2S)-, COMPD. WITH 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 (1:1)
Common Name English
SUNITINIB MALATE [VANDF]
Common Name English
SU-011248 L-MALATE SALT
Code English
SU011248 L-MALATE SALT
Code English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
EMA ASSESSMENT REPORTS SUTENT (AUTHORIZED: CARCINOMA , RENAL CELL)
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
EMA ASSESSMENT REPORTS SUTENT (AUTHORIZED: GASTROINTESTINAL STROMAL TUMORS)
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
NCI_THESAURUS C1967
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
NCI_THESAURUS C1971
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
Code System Code Type Description
CAS
341031-54-7
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
RXCUI
616275
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY RxNorm
NCI_THESAURUS
C26673
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
PUBCHEM
6456015
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
EVMPD
SUB22366
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
EU-Orphan Drug
EU/3/05/268(WITHDRAWN)
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in July 2008 on request of the sponsor. On 10 March 2005, orphan designation (EU/3/05/268) was granted by the European Commission to Pfizer Limited, United Kingdom, for (Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate for the treatment of renal cell carcinoma. (Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate has been authorised in the EU as Sutent since 19 July 2006 for the treatment of advanced and/or metastatic renal cell carcinoma (MRCC) after failure of interferon alfa or interleukin-2 therapy.
EU-Orphan Drug
EU/3/05/267(WITHDRAWN)
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in July 2008 on request of the sponsor. On 10 March 2005, orphan designation (EU/3/05/267) was granted by the European Commission to Pfizer Limited, United Kingdom, for (Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate for the treatment of malignant gastrointestinal stromal tumours. (Z)-N-[2-(Diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate has been authorised in the EU as Sutent since 19 July 2006.
EPA CompTox
341031-54-7
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
ChEMBL
CHEMBL535
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY
MERCK INDEX
M10399
Created by admin on Mon Oct 21 20:36:34 UTC 2019 , Edited by admin on Mon Oct 21 20:36:34 UTC 2019
PRIMARY Merck Index
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY