Identification
- Summary
Sunitinib is a receptor tyrosine kinase inhibitor and chemotherapeutic agent used for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST).
- Brand Names
- Sutent
- Generic Name
- Sunitinib
- DrugBank Accession Number
- DB01268
- Background
Sunitinib is a small-molecule multi-targeted receptor tyrosine kinase (RTK) inhibitor. On January 26, 2006, the agent was formally approved by the US FDA for the indications of treating renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). For these purposes, sunitinib is generally available as an orally administered formulation. 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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Sunitinib (DB01268)
- Weight
- Average: 398.4738
Monoisotopic: 398.211804333 - Chemical Formula
- C22H27FN4O2
- Synonyms
- Sunitinib
- Sunitinibum
- External IDs
- SU-011248
- SU-11248
- SU011248
- SU11248
Pharmacology
- Indication
Sunitinib is indicated for the following conditions:3
- Treatment of adult patients with gastrointestinal stromal tumor (GIST) following disease progression on (or intolerance to) imatinib mesylate
- Treatment of adult patients with advanced renal cell carcinoma (RCC)
- Adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy
- Treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Gastrointestinal stromal tumor (gist) •••••••••••• ••••• ••••••• Prevention of Recurrent renal cell carcinoma •••••••••••• ••••• ••••••• Treatment of Renal cell carcinoma •••••••••••• ••••• ••••••• Treatment of Unresectable, locally advanced progressive neuroendocrine tumors of pancreatic origin •••••••••••• ••••• ••••••• Treatment of Unresectable, metastatic progressive neuroendocrine tumors of pancreatic origin •••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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 UHepatocyte growth factor receptor 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]
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
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 Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Sunitinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Sunitinib can be increased when combined with Abatacept. Abemaciclib Sunitinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Acalabrutinib The metabolism of Sunitinib can be decreased when combined with Acalabrutinib. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Sunitinib. - Food Interactions
- Avoid grapefruit products. Grapefruit may reduce the CYP3A4 metabolism of sunitinib.
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of sunitinib.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Sunitinib malate LVX8N1UT73 341031-54-7 LBWFXVZLPYTWQI-IPOVEDGCSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sunitinib Accord Capsule 50 mg Oral Accord Healthcare S.L.U. 2021-04-20 Not applicable EU 
Sunitinib Accord Capsule 37.5 mg Oral Accord Healthcare S.L.U. 2021-04-20 Not applicable EU Sunitinib Accord Capsule 25 mg Oral Accord Healthcare S.L.U. 2021-04-20 Not applicable EU Sunitinib Accord Capsule 12.5 mg Oral Accord Healthcare S.L.U. 2021-04-20 Not applicable EU Sunitinib Accord Capsule 50 mg Oral Accord Healthcare S.L.U. 2021-04-20 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Auro-sunitinib Capsule 25 mg Oral Auro Pharma Inc 2023-07-21 Not applicable Canada 
Auro-sunitinib Capsule 50 mg Oral Auro Pharma Inc 2023-07-21 Not applicable Canada Auro-sunitinib Capsule 12.5 mg Oral Auro Pharma Inc 2023-09-18 Not applicable Canada Auro-sunitinib Capsule 37.5 mg Oral Auro Pharma Inc Not applicable Not applicable Canada Nat-sunitinib Capsule 50 mg Oral Natco Pharma Limited Not applicable Not applicable Canada
Categories
- ATC Codes
- L01EX01 — Sunitinib
- Drug 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 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Growth Inhibitors
- Growth Substances
- Hepatotoxic Agents
- Heterocyclic Compounds, Fused-Ring
- Hypoglycemia-Associated Agents
- Immunosuppressive Agents
- Indoles
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Potential QTc-Prolonging Agents
- Protein Kinase Inhibitors
- QTc Prolonging Agents
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, pyrroles (CHEBI:38940)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- V99T50803M
- CAS number
- 557795-19-4
- 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
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. [Article]
- 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. [Article]
- FDA Approved Drug Products: Sutent (sunitinib malate) capsules for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0015397
- KEGG Drug
- D06402
- PubChem Compound
- 5329102
- PubChem Substance
- 46507140
- ChemSpider
- 4486264
- BindingDB
- 4814
- 357977
- ChEBI
- 38940
- ChEMBL
- CHEMBL535
- ZINC
- ZINC000003964325
- Therapeutic Targets Database
- DCL000646
- PharmGKB
- PA162372840
- PDBe Ligand
- B49
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Sunitinib
- PDB Entries
- 2y7j / 3g0f / 3ti1 / 4agd / 4ks8 / 4qmz / 6jok / 6m11 / 6nfy / 6nfz … show 2 more
- FDA label
- Download (159 KB)
- MSDS
- Download (98.3 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Other Metastatic Renal Cell Carcinoma ( mRCC) 1 4 Completed Other Well-differentiated Pancreatic Neuroendocrine Tumor 1 4 Completed Treatment Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors 1 4 Completed Treatment Gastrointestinal Stromal Tumor (GIST) / Non-Small Cell Lung Cancer (NSCLC) / Renal Cell Carcinoma (RCC) 1 4 Completed Treatment Refractory Solid Tumors 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Pfizer Inc.
- Dosage Forms
Form Route Strength Capsule Oral 16.71 mg Capsule Oral 12.50 mg Capsule, gelatin coated Oral 12.50 mg Capsule, gelatin coated Oral 25.00 mg Capsule, gelatin coated Oral 37.50 mg Capsule, gelatin coated Oral 50.00 mg Capsule Oral Capsule Oral 25 MG Capsule Oral 37.5 MG Capsule Oral 50 MG Capsule Oral 12.5 mg/1 Capsule Oral 25 mg/1 Capsule Oral 37.5 mg/1 Capsule Oral 50 mg/1 Capsule Oral 12.5 mg Capsule Oral 66.800 mg Capsule, coated Oral 12.5 mg Capsule, coated Oral 25 mg Capsule, coated Oral 66.8 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) Region CA2395461 No 2010-05-25 2020-12-22 Canada CA2399358 No 2006-03-21 2021-02-15 Canada US6573293 Yes 2003-06-03 2021-08-15 US 
US7211600 Yes 2007-05-01 2021-06-22 US US7125905 Yes 2006-10-24 2021-08-15 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 44.74 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 splash10-001r-9043000000-f9288d8cb7c447b10d86 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-b4a0ecc2ede10ff3d215 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-23bc96d60980284515cc Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0569-0094000000-c6a098e6818d1adb40d0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-06r2-3494000000-4f53b610735e4ba586c5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0092000000-c54cd0cd5a35a930d43d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4m-2096000000-2db3b4f39813196c0c6c Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 209.531081 predictedDarkChem Lite v0.1.0 [M-H]- 206.60162 predictedDeepCCS 1.0 (2019) [M+H]+ 210.045181 predictedDarkChem Lite v0.1.0 [M+H]+ 208.95961 predictedDeepCCS 1.0 (2019) [M+Na]+ 211.461681 predictedDarkChem Lite v0.1.0 [M+Na]+ 215.7927 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Joensuu H: Second line therapies for the treatment of gastrointestinal stromal tumor. Curr Opin Oncol. 2007 Jul;19(4):353-8. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- Katoh Y, Katoh M: Comparative integromics on VEGF family members. Int J Oncol. 2006 Jun;28(6):1585-9. [Article]
- 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. [Article]
- Ahmed SI, Thomas AL, Steward WP: Vascular endothelial growth factor (VEGF) inhibition by small molecules. J Chemother. 2004 Nov;16 Suppl 4:59-63. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
- Gene Name
- MET
- Uniprot ID
- P08581
- Uniprot Name
- Hepatocyte growth factor receptor
- Molecular Weight
- 155540.035 Da
References
- Ibrahim HS, Albakri ME, Mahmoud WR, Allam HA, Reda AM, Abdel-Aziz HA: Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase. Bioorg Chem. 2019 Apr;85:337-348. doi: 10.1016/j.bioorg.2019.01.006. Epub 2019 Jan 8. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- Inhibition of CYP3A4 supported by in vitro data only.
- 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. [Article]
- Flockhart Table of Drug Interactions [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
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Flockhart Table of Drug Interactions [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
- Flockhart Table of Drug Interactions [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. [Article]
- 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. [Article]
- 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. [Article]
- Tang SC, Lagas JS, Lankheet NA, Poller B, Hillebrand MJ, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of sunitinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration. Int J Cancer. 2012 Jan 1;130(1):223-33. doi: 10.1002/ijc.26000. Epub 2011 Apr 7. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug created at May 16, 2007 20:11 / Updated at February 20, 2024 23:54