Tìm theo
Vemurafenib
Các tên gọi khác (3) :
  • BRAF(V600E) Kinase Inhibitor RO5185426
  • PLX4032
  • Zelboraf
Thuốc Gốc
Small Molecule
CAS: 918504-65-1
ATC: L01XE15
CTHH: C23H18ClF2N3O3S
PTK: 489.922
Vemurafenib is a BRAF enzyme inhibitor developed by Plexxikon and Genentech for the treatment of late-stage melanoma. [Wikipedia] The cobas® 4800 BRAF B600 mutation test provided by Roche Molecular Systems is the diagnostic test to confirm eligibility for treatment. FDA approved on August 17, 2011 under the company Hoffmann La Roche.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C23H18ClF2N3O3S
Phân tử khối
489.922
Monoisotopic mass
489.072546264
InChI
InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)
InChI Key
InChIKey=GPXBXXGIAQBQNI-UHFFFAOYSA-N
IUPAC Name
N-{3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide
Traditional IUPAC Name
vemurafenib
SMILES
CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C2=CC=C(Cl)C=C2)=C(F)C=C1
Độ tan chảy
272°C
Độ hòa tan
<1 mg/mL
logP
5.1
logS
-6.1
pKa (strongest acidic)
7.17
pKa (Strongest Basic)
3.2
PSA
91.92 Å2
Refractivity
121.97 m3·mol-1
Polarizability
48.1 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
4
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Cơ Chế Tác Dụng : Vemurafenib is a BRAF enzyme inhibitor developed by Plexxikon and Genentech for the treatment of late-stage melanoma. [Wikipedia] The cobas® 4800 BRAF B600 mutation test provided by Roche Molecular Systems is the diagnostic test to confirm eligibility for treatment. FDA approved on August 17, 2011 under the company Hoffmann La Roche. Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. It is especially potent against the BRAF V600E mutation. This mutation involves the substitution of glutamic acid for valine at codon 600. The BRAF oncogene, most of which have the V600E mutation, activates mitogen-activated kinase (MAPK) pathway which results in cell growth, proliferation, and metastasis. Vemurafenib blocks these downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenib does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.
Dược Động Học :
▧ Absorption :
After oral administration of vemurafenib, it is well absorbed. Bioavailability is unknown. Peak concentrations are reached in 3 hours when an oral dose of 960 mg twice daily for 15 days has been given to patients. Exposure is highly variable between different patients. Gastrointestinal fluid content, pH, volumes, motility, transition time and bile composition may be factors affecting exposure. It is unknown how food affects the absorption of vemurafenib. Time to steady state = 15 - 22 days
▧ Volume of Distribution :
106 L
▧ Protein binding :
>99% protein bound to serum albumin and alpha-1 acid glycoprotein.
▧ Metabolism :
Vemurafenib is metabolized by CYP3A4 and the metabolites make up 5% of the components in plasma. The parent compound makes up for the remaining 95%.
▧ Route of Elimination :
Excreted via feces (94%) and urine (1%).
▧ Half Life :
Elimination half-life = 57 hours (range of 30-120 hours)
▧ Clearance :
Total body clearance = 31 L/day
Chỉ Định : Treatment of unresectable or metastatic melanoma in patients with the BRAF-V600 mutation.
Tương Tác Thuốc :
  • Atazanavir Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Caffeine Vemurafenib increases the AUC of caffeine (CYP1A2 substrate) 2.6-fold.
  • Carbamazepine Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Clarithromycin Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Dextromethorphan Vemurafenib increases the AUC (CYP2D6 substrate) by 47% .
  • Indinavir Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Ipilimumab Consider therapy modification due to enhanced hepatotoxicity of vemurafenib
  • Itraconazole Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Ketoconazole Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Midazolam Vemurafenib decreases the AUC (CYP3A4 substrate) by 39%.
  • Nefazodone Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Nelfinavir Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Phenobarbital Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Phenytoin Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Rifabutin Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Rifampicin Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Rifapentine Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
  • Ritonavir Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Saquinavir Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Telithromycin Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Voriconazole Strong CYP3A4 inhibitors may increase levels of vemurafenib. Monitor concomitant therapy closely.
  • Warfarin Vemurafenib increases the AUC of S-warfarin (CYP2C9 substrate). Monitor concomitant therapy closely.
Liều Lượng & Cách Dùng : Tablet - Oral - 240 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08881
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09996
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50242-090-01
PharmGKB
http://www.pharmgkb.org/drug/PA165946873
Wikipedia
http://en.wikipedia.org/wiki/Vemurafenib
RxList
http://www.rxlist.com/zelboraf-drug.htm
Drugs.com
http://www.drugs.com/mtm/vemurafenib.html
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