Tìm theo
Vandetanib
Các tên gọi khác (7 ) :
  • 4-BROMO-2-fluoro-N-[(4e)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4(1H)-ylidene]aniline
  • 4-quinazolinamine, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-
  • N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
  • Zactima
  • ZD 6474
  • ZD6474
Thuốc Gốc
Small Molecule
CAS: 443913-73-3
ATC: L01XE12
CTHH: C22H24BrFN4O2
PTK: 475.354
Vandetanib is an oral once-daily kinase inhibitor of tumour angiogenesis and tumour cell proliferation with the potential for use in a broad range of tumour types. On April 6 2011, vandetanib was approved by the FDA to treat nonresectable, locally advanced, or metastatic medullary thyroid cancer in adult patients.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H24BrFN4O2
Phân tử khối
475.354
Monoisotopic mass
474.106666884
InChI
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
InChI Key
InChIKey=UHTHHESEBZOYNR-UHFFFAOYSA-N
IUPAC Name
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
Traditional IUPAC Name
vandetanib
SMILES
COC1=C(OCC2CCN(C)CC2)C=C2N=CN=C(NC3=C(F)C=C(Br)C=C3)C2=C1
Độ hòa tan
0.008 mg/mL at 25°C (77°F )
logP
4.54
logS
-4.7
pKa (strongest acidic)
13.8
pKa (Strongest Basic)
9.13
PSA
59.51 Å2
Refractivity
118.63 m3·mol-1
Polarizability
47.1 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
6
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Mean IC50 of approximately 2.1 μg/mL.
Cơ Chế Tác Dụng : Vandetanib is an oral once-daily kinase inhibitor of tumour angiogenesis and tumour cell proliferation with the potential for use in a broad range of tumour types. On April 6 2011, vandetanib was approved by the FDA to treat nonresectable, locally advanced, or metastatic medullary thyroid cancer in adult patients. ZD-6474 is a potent and selective inhibitor of VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor) and RET (REarranged during Transfection) tyrosine kinases. VEGFR- and EGFR-dependent signalling are both clinically validated pathways in cancer, including non-small-cell lung cancer (NSCLC). RET activity is important in some types of thyroid cancer, and early data with vandetanib in medullary thyroid cancer has led to orphan-drug designation by the regulatory authorities in the USA and EU.
Dược Động Học :
▧ Absorption :
Slow- peak plasma concentrations reached at a median 6 hours. On multiple dosing, Vandetanib accumulates about 8 fold with steady state reached after around 3 months.
▧ Volume of Distribution :
Vd of about 7450 L.
▧ Protein binding :
Protein binding of about 90%.
▧ Metabolism :
Unchanged vandentanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. N-desmethyl-vandetanib is primarily produced by CYP3A4, and vandetanib-N-oxide is primarily produced by flavin–containing monooxygenase enzymes FMO1 and FMO3.
▧ Route of Elimination :
About 69% was recovered following 21 days after a single dose of vandentanib. 44% was found in feces and 25% in urine.
▧ Half Life :
Median half life of 19 days.
Chỉ Định : Vandetanib is currently approved as an alternative to local therapies for both unresectable and disseminated disease. Because Vandetanib can prolong the Q-T interval, it is contraindicated for use in patients with serious cardiac complications such as congenital long QT syndrome and uncompensated heart failure.
Tương Tác Thuốc :
  • Bosentan Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Carbamazepine Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Dexamethasone Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Efavirenz Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Etravirine Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Fosphenytoin Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Nafcillin Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Nevirapine Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Pentobarbital Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Phenobarbital Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Phenytoin Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Primidone Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Rifabutin Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Rifampicin Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • Rifapentine Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
  • St. John's Wort Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
Liều Lượng & Cách Dùng : Tablet, film coated - Oral - white, oval, biconvex, 300-mg tablets
Tablet, film coated - Oral - white, round, biconvex, 100-mg tablets
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Caprelsa
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Zactima
  • Công ty : AstraZeneca
    Sản phẩm biệt dược : Zictifa
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05294
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06407
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=4655
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/00310-7830-30
Wikipedia
http://en.wikipedia.org/wiki/Vandetanib
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