Tìm theo
Sorafenib
Các tên gọi khác (3) :
  • 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide
  • N-(4-Chloro-3-(trifluoromethyl)phenyl)-n'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea
  • Sorafenibum
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 284461-73-0
ATC: L01XE05
ĐG : Bayer Healthcare , http://www.bayerhealthcare.com
CTHH: C21H16ClF3N4O3
PTK: 464.825
Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials. Sorafenib is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C21H16ClF3N4O3
Phân tử khối
464.825
Monoisotopic mass
464.08630272
InChI
InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
InChI Key
InChIKey=MLDQJTXFUGDVEO-UHFFFAOYSA-N
IUPAC Name
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
Traditional IUPAC Name
sorafenib
SMILES
CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Độ hòa tan
Insoluble
logP
3.8
logS
-5.4
pKa (strongest acidic)
11.55
pKa (Strongest Basic)
2.03
PSA
92.35 Å2
Refractivity
114.52 m3·mol-1
Polarizability
41.11 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
3
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : No large changes in QTc interval were observed. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2.
Cơ Chế Tác Dụng : Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials. Sorafenib is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway. Sorafenib interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in angiogenesis, thus sorafenib reduces blood flow to the tumor. Sorafenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.
Dược Động Học :
▧ Absorption :
The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. Sorafenib reached peak plasma levels in 3 hours following oral administration. With a high-fat meal, bioavailability is reduced by 29% compared to administration in the fasted state.
▧ Protein binding :
99.5% bound to plasma proteins.
▧ Metabolism :
Sorafenib is metabolized primarily in the liver, undergoing oxidative metabolism, mediated by CYP3A4, as well as glucuronidation mediated by UGT1A9. Sorafenib accounts for approximately 70-85% of the circulating analytes in plasma at steady- state. Eight metabolites of sorafenib have been identified, of which five have been detected in plasma. The main circulating metabolite of sorafenib in plasma, the pyridine N-oxide, shows in vitro potency similar to that of sorafenib. This metabolite comprises approximately 9-16% of circulating analytes at steady-state.
▧ Route of Elimination :
Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in feces, and 19% of the dose excreted in urine as glucuronidated metabolites.
▧ Half Life :
25-48 hours
Độc Tính : The highest dose of sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic events. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals.
Chỉ Định : Sorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma.
Tương Tác Thuốc :
  • Bevacizumab Monitor therapy due to increased adverse effects of sorafenib, especially hand-foot skin reaction.
  • Carboplatin Sorafenib may enhance the adverse/toxic effect of carboplatin. Concurrent use of sorafenib with carboplatin and placlitaxel in patients with squamous cell lung cancer is contraindicated. The use of this combination in other settings is not specifically contraindicated, but any such use should be approached with added caution.
  • Etravirine Sorafebib, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Tretinoin The strong CYP2C8 inhibitor, Sorafenib, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Sorafenib is initiated, discontinued to dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 200 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Nexavar 200 mg tablet
    Giá bán buôn : USD >66.61
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Nexavar
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00398
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=216239
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505329
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08524
ChemSpider
http://www.chemspider.com/Chemical-Structure.187440.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=16673
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50419-488-58
PharmGKB
http://www.pharmgkb.org/drug/PA7000
Wikipedia
http://en.wikipedia.org/wiki/Sorafenib
RxList
http://www.rxlist.com/nexavar-drug.htm
Drugs.com
http://www.drugs.com/cdi/sorafenib.html
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