Tìm theo
Vismodegib
Các tên gọi khác (4 ) :
  • Erivedge
  • GDC-0449
  • Hedgehog Antagonist GDC-0449
  • Vismodegibum
Thuốc Gốc
Small Molecule
CAS: 879085-55-9
ATC: L01XX43
CTHH: C19H14Cl2N2O3S
PTK: 421.297
Vismodegib inhibits the hedgehog signalling pathway and is indicated for treatment of adult basal cell carcinoma. FDA approved on Jan 30, 2012.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H14Cl2N2O3S
Phân tử khối
421.297
Monoisotopic mass
420.010218428
InChI
InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)
InChI Key
InChIKey=BPQMGSKTAYIVFO-UHFFFAOYSA-N
IUPAC Name
2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-methanesulfonylbenzamide
Traditional IUPAC Name
vismodegib
SMILES
CS(=O)(=O)C1=CC(Cl)=C(C=C1)C(=O)NC1=CC=C(Cl)C(=C1)C1=CC=CC=N1
Độ hòa tan
0.1 μg/mL and is pH dependent
logP
2.7
logS
-5.4
pKa (strongest acidic)
10.27
pKa (Strongest Basic)
3.7
PSA
76.13 Å2
Refractivity
107.81 m3·mol-1
Polarizability
39.49 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
3.8
Dược Lực Học : Vismodegib selectively binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.
Cơ Chế Tác Dụng : Vismodegib inhibits the hedgehog signalling pathway and is indicated for treatment of adult basal cell carcinoma. FDA approved on Jan 30, 2012. Mutations of the Hedgehog pathway may results in uncontrolled proliferation of skin basal cells. Vismodegib binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.
Dược Động Học :
▧ Absorption :
The absolute bioavailability of a single dose is 31.8%. Absorption is saturable and is not affected by food.
▧ Volume of Distribution :
Vismodegib has a volume of distribution of 16.4 to 26.6 L.
▧ Protein binding :
Vismodegib is highly protein bound with plasma protein binding at about 99%. Vismodegib binds to the plasma proteins, albumin and alpha-1-acid glycoprotein (saturable bnding).
▧ Metabolism :
The main metabolic enzymes are CYP2C9 and CYP3A4, however more than 98% of total systemic vismodegib is not metabolized. Metabolic pathways of vismodegib in humans include oxidation, glucuronidation, and pyridine ring cleavage. The two most abundant oxidative metabolites recovered in feces are produced in vitro by recombinant CYP2C9 and CYP3A4/5.
▧ Route of Elimination :
Vismodegib is mostly excreted unchanged, and the main route of elimination is by the feces (82%) and the urine accounts for 4.4%.
▧ Half Life :
The half-life after a single dose is 12 days, and after continuous daily dosing is 4 days.
Độc Tính : Increased risk of embryo-fetal death and significant birth defects. Common adverse event include muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.
Chỉ Định : Vismodegib is used for treating locally advanced or metastatic basal cell carcinoma in patients whose carcinoma has recurred after surgery, and in patients who are not candidates for surgery or radiation.
Tương Tác Thuốc :
  • Azithromycin P-glycoprotein inhibitors may increase the chance of adverse drug reactions.
  • Clarithromycin P-glycoprotein inhibitors may increase the chance of adverse drug reactions.
  • Erythromycin P-glycoprotein inhibitors may increase the chance of adverse drug reactions.
  • Ivacaftor P-glycoprotein inhibitors may increase the chance of adverse drug reactions. Consider using alternative therapy.
  • Omeprazole Vismodegib serum concentrations may be decreased by proton pump inhibitors such as omeprazole.
  • Ranitidine Vismodegib serum concentrations may be decreased by histamine 2 receptor antagonists such as ranitidine.
Liều Lượng & Cách Dùng : Capsule - Oral - 150 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Genentech
    Sản phẩm biệt dược : Erivedge
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08828
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09992
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50242-140-01
PharmGKB
http://www.pharmgkb.org/drug/PA166048558
Wikipedia
http://en.wikipedia.org/wiki/Vismodegib
RxList
http://www.rxlist.com/erivedge-drug.htm
Drugs.com
http://www.drugs.com/mtm/vismodegib.html
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