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Details

Stereochemistry ACHIRAL
Molecular Formula C22H27FN4O2.C4H4O4
Molecular Weight 514.5459
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of SUNITINIB MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=CC=C(F)C=C23)=C1C

InChI

InChIKey=XGQXULJHBWKUJY-LYIKAWCPSA-N
InChI=1S/C22H27FN4O2.C4H4O4/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;5-3(6)1-2-4(7)8/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28);1-2H,(H,5,6)(H,7,8)/b17-12-;2-1-

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 C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
Fatal liver failure in a patient on acetaminophen treated with sunitinib malate and levothyroxine.
2009 Apr
Sequential sorafenib and sunitinib for renal cell carcinoma.
2009 Jul
Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2.
2009 Jun 28
Novel agents for renal cell carcinoma require novel selection paradigms to optimise first-line therapy.
2009 May
The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity.
2010 Apr 15
Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity.
2010 Aug
Synthesis and structure-activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors.
2010 Jul 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
Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.
2011 Jun
Sunitinib improves chemotherapeutic efficacy and ameliorates cisplatin-induced nephrotoxicity in experimental animals.
2011 May
Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.
2011 Nov 15
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011 Oct 30
Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells.
2012 Jul
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
A high-throughput screen for teratogens using human pluripotent stem cells.
2014 Jan
Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs.
2014 Jan 15
Development of cardiac hypertrophy by sunitinib in vivo and in vitro rat cardiomyocytes is influenced by the aryl hydrocarbon receptor signaling pathway.
2014 Mar
Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma.
2015 Dec
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 Tue Oct 22 18:12:24 UTC 2019
Edited
by admin
on Tue Oct 22 18:12:24 UTC 2019
Record UNII
92019DWI1D
Record Status Validated (UNII)
Record Version
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Name Type Language
SUNITINIB MALEATE
Common Name 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-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
Code System Code Type Description
CAS
1126641-10-8
Created by admin on Tue Oct 22 18:12:24 UTC 2019 , Edited by admin on Tue Oct 22 18:12:24 UTC 2019
PRIMARY
PUBCHEM
16113195
Created by admin on Tue Oct 22 18:12:24 UTC 2019 , Edited by admin on Tue Oct 22 18:12:24 UTC 2019
PRIMARY
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