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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Sunitinib
- Accession Number
- DB01268 (DB07417)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib inhibits cellular signaling by targeting multiple RTKs. These include all platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R). Sunitinib also inhibits KIT (CD117), the RTK that drives the majority of GISTs. In addition, sunitinib inhibits other RTKs including RET, CSF-1R, and flt3.
- Structure
Structure for Sunitinib (DB01268)
- Synonyms
- Sunitinib
- Sunitinibum
- External IDs
- SU-011248 / SU-11248 / SU011248 / SU11248
- Product Ingredients
Ingredient UNII CAS InChI Key Sunitinib malate LVX8N1UT73 341031-54-7 LBWFXVZLPYTWQI-IPOVEDGCSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Sutent Capsule 12.5 mg Oral Pfizer 2006-07-19 Not applicable EU 
Sutent Capsule 37.5 mg Oral Pfizer Not applicable Not applicable Canada 
Sutent Capsule 50 mg/1 Oral Pfizer Laboratories Div Pfizer Inc. 2006-01-26 Not applicable US 
Sutent Capsule 37.5 mg Oral Pfizer 2006-07-19 Not applicable EU Sutent Capsule 50 mg Oral Pfizer 2006-07-19 Not applicable EU Sutent Capsule 50 mg Oral Pfizer 2006-06-22 Not applicable Canada Sutent Capsule 25 mg/1 Oral Pfizer Laboratories Div Pfizer Inc. 2006-01-26 Not applicable US Sutent Capsule 50 mg Oral Pfizer 2006-07-19 Not applicable EU Sutent Capsule 25 mg Oral Pfizer 2006-07-19 Not applicable EU Sutent Capsule 25 mg Oral Pfizer 2006-06-22 Not applicable Canada - Categories
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Blood Glucose Lowering Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Growth Inhibitors
- Growth Substances
- Hypoglycemia-Associated Agents
- Immunosuppressive Agents
- Kinase Inhibitor
- P-glycoprotein/ABCB1 Inhibitors
- P-glycoprotein/ABCB1 Substrates
- Potential QTc-Prolonging Agents
- Protein Kinase Inhibitors
- QTc Prolonging Agents
- Tyrosine Kinase Inhibitors
- UNII
- V99T50803M
- CAS number
- 557795-19-4
- Weight
- Average: 398.4738
Monoisotopic: 398.211804333 - Chemical Formula
- C22H27FN4O2
- InChI Key
- WINHZLLDWRZWRT-ATVHPVEESA-N
- InChI
- 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-
- IUPAC Name
- N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide
- SMILES
- CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C
Pharmacology
- Indication
For the treatment of advanced renal cell carcinoma as well as the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.
- Associated Conditions
- Pharmacodynamics
Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
- Mechanism of action
Sunitinib is a small molecule that inhibits multiple RTKs, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 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 inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
Target Actions Organism APlatelet-derived growth factor receptor beta inhibitorHumans AVascular endothelial growth factor receptor 1 inhibitorHumans AMast/stem cell growth factor receptor Kit inhibitorHumans AVascular endothelial growth factor receptor 2 inhibitorHumans AVascular endothelial growth factor receptor 3 inhibitorHumans AReceptor-type tyrosine-protein kinase FLT3 inhibitorHumans AMacrophage colony-stimulating factor 1 receptor inhibitorHumans APlatelet-derived growth factor receptor alpha inhibitorHumans - Absorption
Maximum plasma concentrations (Cmax) of sunitinib are generally observed between 6 and 12 hours (Tmax) following oral administration. Food has no effect on the bioavailability of sunitinib. Sunitinib may be taken with or without food. The pharmacokinetics were similar in healthy volunteers and in the solid tumor patient populations tested, including patients with GIST and RCC.
- Volume of distribution
- 2230 L (apparent volume of distribution, Vd/F)
- Protein binding
Binding of sunitinib and its primary metabolite to human plasma protein in vitro was 95% and 90%, respectively.
- Metabolism
Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4.
- Route of elimination
Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4. Elimination is primarily via feces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in feces, with renal elimination accounting for 16% of the administered dose.
- Half life
Following administration of a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its primary active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.
- Clearance
- 34 - 62 L/h [Total oral clearance]
- Toxicity
The maximally tolerated dose for rat, mouse, and dog when given orally is greater than 500 mg/kg. The maximally tolerated dose of a non-human primate is greater 1200 mg/kg.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 3A4 --- (A;A) / (A;G) G > A ADR Directly Studied Patients with metastatic renal cell carcinoma who carry this polymorphism in CYP3A4 are at a higher risk of experiencing drug-induced hypertension when treated with sunitinib. Details
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Sunitinib. (S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Sunitinib. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Sunitinib is combined with 2-Methoxyethanol. 2,4-thiazolidinedione The risk or severity of hypoglycemia can be increased when Sunitinib is combined with 2,4-thiazolidinedione. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Sunitinib. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Sunitinib. 5-(2-methylpiperazine-1-sulfonyl)isoquinoline The therapeutic efficacy of Sunitinib can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline. 5-androstenedione The metabolism of 5-androstenedione can be decreased when combined with Sunitinib. 5-Fluorouridine The risk or severity of QTc prolongation can be increased when 5-Fluorouridine is combined with Sunitinib. 6-Deoxyerythronolide B The metabolism of Sunitinib can be decreased when combined with 6-Deoxyerythronolide B. - Food Interactions
- Not Available
References
- Synthesis Reference
Ettore BIGATTI, Augusto CANAVESI, Peter Lindsay MACDONALD, Francesca Scarpitta, "PROCESSES FOR PREPARING SUNITINIB AND SALTS THEREOF." U.S. Patent US20090247767, issued October 01, 2009.
US20090247767- General References
- Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. [PubMed:17215529]
- Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. [PubMed:17046465]
- External Links
- Human Metabolome Database
- HMDB0015397
- KEGG Drug
- D06402
- PubChem Compound
- 5329102
- PubChem Substance
- 46507140
- BindingDB
- 4814
- ChEBI
- 38940
- ChEMBL
- CHEMBL535
- Therapeutic Targets Database
- DCL000646
- PharmGKB
- PA162372840
- HET
- B49
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Sunitinib
- ATC Codes
- L01XE04 — Sunitinib
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- PDB Entries
- 2y7j / 3g0e / 3g0f / 3miy / 3ti1 / 4agd / 4ks8 / 4qmz
- FDA label
- Download (159 KB)
- MSDS
- Download (98.3 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Pfizer Inc.
- Dosage forms
Form Route Strength Capsule Oral 12.5 mg/1 Capsule Oral 12.5 mg Capsule Oral 25 mg/1 Capsule Oral 25 mg Capsule Oral 37.5 mg/1 Capsule Oral 37.5 mg Capsule Oral 50 mg/1 Capsule Oral 50 mg - Prices
Unit description Cost Unit Sutent 50 mg capsule 333.39USD capsule Sutent 25 mg capsule 187.28USD capsule Sutent 12.5 mg capsule 93.64USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) CA2395461 No 2010-05-25 2020-12-22 Canada CA2399358 No 2006-03-21 2021-02-15 Canada US6573293 No 2003-06-03 2021-02-15 US US7211600 No 2007-05-01 2020-12-22 US US7125905 No 2006-10-24 2021-02-15 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility >25 mg/mL over pH of 1.2 to 6.8 FDA label logP 5.2 FDA label pKa 8.95 FDA label - Predicted Properties
Property Value Source Water Solubility 0.0308 mg/mL ALOGPS logP 3.24 ALOGPS logP 2.93 ChemAxon logS -4.1 ALOGPS pKa (Strongest Acidic) 11.46 ChemAxon pKa (Strongest Basic) 9.04 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 77.23 Å2 ChemAxon Rotatable Bond Count 7 ChemAxon Refractivity 116.27 m3·mol-1 ChemAxon Polarizability 44.32 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9938 Blood Brain Barrier + 0.7993 Caco-2 permeable - 0.5948 P-glycoprotein substrate Substrate 0.8648 P-glycoprotein inhibitor I Inhibitor 0.6809 P-glycoprotein inhibitor II Non-inhibitor 0.5466 Renal organic cation transporter Non-inhibitor 0.7385 CYP450 2C9 substrate Non-substrate 0.8727 CYP450 2D6 substrate Non-substrate 0.7716 CYP450 3A4 substrate Substrate 0.641 CYP450 1A2 substrate Non-inhibitor 0.5626 CYP450 2C9 inhibitor Non-inhibitor 0.6437 CYP450 2D6 inhibitor Non-inhibitor 0.6846 CYP450 2C19 inhibitor Non-inhibitor 0.6261 CYP450 3A4 inhibitor Non-inhibitor 0.5991 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7032 Ames test Non AMES toxic 0.5699 Carcinogenicity Non-carcinogens 0.784 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6794 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8597 hERG inhibition (predictor II) Inhibitor 0.8398
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indolines
- Direct Parent
- Indolines
- Alternative Parents
- Pyrrole carboxamides / Substituted pyrroles / Aryl fluorides / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Lactams show 6 more
- Substituents
- Dihydroindole / Pyrrole-3-carboxamide / Pyrrole-3-carboxylic acid or derivatives / Aryl fluoride / Aryl halide / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Vinylogous amide show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, pyrroles (CHEBI:38940)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor binding
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
- Gene Name
- PDGFRB
- Uniprot ID
- P09619
- Uniprot Name
- Platelet-derived growth factor receptor beta
- Molecular Weight
- 123966.895 Da
References
- Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM: 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. Clin Cancer Res. 2003 Jan;9(1):327-37. [PubMed:12538485]
- Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM: SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003 May;2(5):471-8. [PubMed:12748309]
- Baratte S, Sarati S, Frigerio E, James CA, Ye C, Zhang Q: Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J Chromatogr A. 2004 Jan 23;1024(1-2):87-94. [PubMed:14753710]
- Pietras K, Hanahan D: A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005 Feb 10;23(5):939-52. Epub 2004 Nov 22. [PubMed:15557593]
- Gollob JA: Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma. Clin Genitourin Cancer. 2005 Dec;4(3):167-74. [PubMed:16425993]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vegf-b-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
- Gene Name
- FLT1
- Uniprot ID
- P17948
- Uniprot Name
- Vascular endothelial growth factor receptor 1
- Molecular Weight
- 150767.185 Da
References
- O'Farrell AM, Foran JM, Fiedler W, Serve H, Paquette RL, Cooper MA, Yuen HA, Louie SG, Kim H, Nicholas S, Heinrich MC, Berdel WE, Bello C, Jacobs M, Scigalla P, Manning WC, Kelsey S, Cherrington JM: An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. Clin Cancer Res. 2003 Nov 15;9(15):5465-76. [PubMed:14654525]
- Roskoski R Jr: Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007 May 4;356(2):323-8. Epub 2007 Mar 7. [PubMed:17367763]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
- Gene Name
- KIT
- Uniprot ID
- P10721
- Uniprot Name
- Mast/stem cell growth factor receptor Kit
- Molecular Weight
- 109863.655 Da
References
- Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM: SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003 May;2(5):471-8. [PubMed:12748309]
- Schueneman AJ, Himmelfarb E, Geng L, Tan J, Donnelly E, Mendel D, McMahon G, Hallahan DE: SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res. 2003 Jul 15;63(14):4009-16. [PubMed:12873999]
- Joensuu H: Second line therapies for the treatment of gastrointestinal stromal tumor. Curr Opin Oncol. 2007 Jul;19(4):353-8. [PubMed:17545799]
- Baratte S, Sarati S, Frigerio E, James CA, Ye C, Zhang Q: Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J Chromatogr A. 2004 Jan 23;1024(1-2):87-94. [PubMed:14753710]
- Roskoski R Jr: Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007 May 4;356(2):323-8. Epub 2007 Mar 7. [PubMed:17367763]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM: 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. Clin Cancer Res. 2003 Jan;9(1):327-37. [PubMed:12538485]
- Schueneman AJ, Himmelfarb E, Geng L, Tan J, Donnelly E, Mendel D, McMahon G, Hallahan DE: SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res. 2003 Jul 15;63(14):4009-16. [PubMed:12873999]
- Baratte S, Sarati S, Frigerio E, James CA, Ye C, Zhang Q: Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J Chromatogr A. 2004 Jan 23;1024(1-2):87-94. [PubMed:14753710]
- Schoffski P, Dumez H, Clement P, Hoeben A, Prenen H, Wolter P, Joniau S, Roskams T, Van Poppel H: Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review. Ann Oncol. 2006 Aug;17(8):1185-96. Epub 2006 Jan 17. [PubMed:16418310]
- Amino N, Ideyama Y, Yamano M, Kuromitsu S, Tajinda K, Samizu K, Hisamichi H, Matsuhisa A, Shirasuna K, Kudoh M, Shibasaki M: YM-359445, an orally bioavailable vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, has highly potent antitumor activity against established tumors. Clin Cancer Res. 2006 Mar 1;12(5):1630-8. [PubMed:16533791]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
- Gene Name
- FLT4
- Uniprot ID
- P35916
- Uniprot Name
- Vascular endothelial growth factor receptor 3
- Molecular Weight
- 152755.94 Da
References
- Roskoski R Jr: Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007 May 4;356(2):323-8. Epub 2007 Mar 7. [PubMed:17367763]
- Deprimo SE, Bello CL, Smeraglia J, Baum CM, Spinella D, Rini BI, Michaelson MD, Motzer RJ: Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med. 2007 Jul 2;5:32. [PubMed:17605814]
- Katoh Y, Katoh M: Comparative integromics on VEGF family members. Int J Oncol. 2006 Jun;28(6):1585-9. [PubMed:16685460]
- Gridelli C, Maione P, Del Gaizo F, Colantuoni G, Guerriero C, Ferrara C, Nicolella D, Comunale D, De Vita A, Rossi A: Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007 Feb;12(2):191-200. [PubMed:17296815]
- Ahmed SI, Thomas AL, Steward WP: Vascular endothelial growth factor (VEGF) inhibition by small molecules. J Chemother. 2004 Nov;16 Suppl 4:59-63. [PubMed:15688612]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
- Gene Name
- FLT3
- Uniprot ID
- P36888
- Uniprot Name
- Receptor-type tyrosine-protein kinase FLT3
- Molecular Weight
- 112902.51 Da
References
- O'Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM: SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. Epub 2003 Jan 16. [PubMed:12531805]
- O'Farrell AM, Foran JM, Fiedler W, Serve H, Paquette RL, Cooper MA, Yuen HA, Louie SG, Kim H, Nicholas S, Heinrich MC, Berdel WE, Bello C, Jacobs M, Scigalla P, Manning WC, Kelsey S, Cherrington JM: An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. Clin Cancer Res. 2003 Nov 15;9(15):5465-76. [PubMed:14654525]
- Baratte S, Sarati S, Frigerio E, James CA, Ye C, Zhang Q: Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J Chromatogr A. 2004 Jan 23;1024(1-2):87-94. [PubMed:14753710]
- Schmidt-Arras D, Schwable J, Bohmer FD, Serve H: Flt3 receptor tyrosine kinase as a drug target in leukemia. Curr Pharm Des. 2004;10(16):1867-83. [PubMed:15180525]
- Yee KW, Schittenhelm M, O'Farrell AM, Town AR, McGreevey L, Bainbridge T, Cherrington JM, Heinrich MC: Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells. Blood. 2004 Dec 15;104(13):4202-9. Epub 2004 Aug 10. [PubMed:15304385]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein homodimerization activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor ...
- Gene Name
- CSF1R
- Uniprot ID
- P07333
- Uniprot Name
- Macrophage colony-stimulating factor 1 receptor
- Molecular Weight
- 107982.955 Da
References
- Guo J, Marcotte PA, McCall JO, Dai Y, Pease LJ, Michaelides MR, Davidsen SK, Glaser KB: Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors. Mol Cancer Ther. 2006 Apr;5(4):1007-13. [PubMed:16648572]
- Roskoski R Jr: Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007 May 4;356(2):323-8. Epub 2007 Mar 7. [PubMed:17367763]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
- Gene Name
- PDGFRA
- Uniprot ID
- P16234
- Uniprot Name
- Platelet-derived growth factor receptor alpha
- Molecular Weight
- 122668.46 Da
References
- Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schoffski P, Van Oosterom A, Marynen P, Debiec-Rychter M: Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res. 2006 Apr 15;12(8):2622-7. [PubMed:16638875]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [PubMed:24713129]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Atpase activity, coupled to transmembrane movement of substances
- Specific Function
- May be an organic anion pump relevant to cellular detoxification.
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- Multidrug resistance-associated protein 4
- Molecular Weight
- 149525.33 Da
References
- Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
- Shukla S, Robey RW, Bates SE, Ambudkar SV: Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009 Feb;37(2):359-65. doi: 10.1124/dmd.108.024612. Epub 2008 Oct 29. [PubMed:18971320]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
- Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [PubMed:19232821]
- Shukla S, Robey RW, Bates SE, Ambudkar SV: Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009 Feb;37(2):359-65. doi: 10.1124/dmd.108.024612. Epub 2008 Oct 29. [PubMed:18971320]
Drug created on May 16, 2007 14:11 / Updated on February 18, 2019 20:23