Tìm theo
Sunitinib
Các tên gọi khác (4 ) :
  • SU-11248
  • Sunitinib
  • Sunitinibum
  • Sutent
Thuốc Gốc
Small Molecule
CAS: 557795-19-4
ATC: L01XE04
ĐG : Pfizer Inc. , http://www.pfizer.com
CTHH: C22H27FN4O2
PTK: 398.4738
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H27FN4O2
Phân tử khối
398.4738
Monoisotopic mass
398.211804333
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-
InChI Key
InChIKey=WINHZLLDWRZWRT-ATVHPVEESA-N
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
Traditional IUPAC Name
sunitinib
SMILES
CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C
Độ hòa tan
>25 mg/mL over pH of 1.2 to 6.8
logP
5.2
logS
-4.1
pKa (strongest acidic)
11.46
pKa (Strongest Basic)
9.04
PSA
77.23 Å2
Refractivity
116.27 m3·mol-1
Polarizability
44.32 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
3
H Bond Donor Count
3
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
pKa
8.95
Dược Lực Học : Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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]
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir Possible increase in sunitinib levels
  • Bevacizumab Sunitinib may enhance the adverse/toxic effect of bevacizumab. Specifically, the risk for a specific form of anemia, microangiopathic hemolytic anemia (MAHA), may be increased. Bevacizumab may enhance the hypertensive effect of sunitinib. This combination is contraindicated.
  • Carbamazepine Possible decrease in sunitinib levels
  • Clarithromycin Possible increase in sunitinib levels
  • Dexamethasone Possible decrease in sunitinib levels
  • Indinavir Possible increase in sunitinib levels
  • Itraconazole Possible increase in sunitinib levels
  • Ketoconazole Possible increase in sunitinib levels
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Nefazodone Possible increase in sunitinib levels
  • Nelfinavir Possible increase in sunitinib levels
  • Phenobarbital Possible decrease in sunitinib levels
  • Phenytoin Possible decrease in sunitinib levels
  • Rifabutin Possible decrease in sunitinib levels
  • Rifampicin Possible decrease in sunitinib levels
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Telithromycin Telithromycin may reduce clearance of Sunitinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sunitinib if Telithromycin is initiated, discontinued or dose changed.
  • Temsirolimus Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Topotecan The p-glycoprotein inhibitor, Sunitinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sunitinib by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of sunitinib if voriconazole is initiated, discontinued or dose changed.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Capsule - Oral - 12.5 mg, 25 mg, 50 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Sutent 12.5 mg capsule
    Giá bán buôn : USD >93.64
    Đơn vị tính : capsule
  • Biệt dược thương mại : Sutent 25 mg capsule
    Giá bán buôn : USD >187.28
    Đơn vị tính : capsule
  • Biệt dược thương mại : Sutent 50 mg capsule
    Giá bán buôn : USD >333.39
    Đơn vị tính : capsule
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Sutent
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01268
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5329102
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507140
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06402
ChemSpider
http://www.chemspider.com/Chemical-Structure.4486264.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=4814
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0069-0550-38
PharmGKB
http://www.pharmgkb.org/drug/PA162372840
Wikipedia
http://en.wikipedia.org/wiki/Sunitinib
RxList
http://www.rxlist.com/cgi/generic/sutent.htm
Drugs.com
http://www.drugs.com/cdi/sunitinib.html
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