Tìm theo
Bosutinib
Các tên gọi khác (6 ) :
  • 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile
  • Bosulif®
  • Bosutinib
  • Bosutinib Monohydrate
  • SKI 606
  • SKI-606
Thuốc Gốc
Small Molecule
CAS: 380843-75-4
ATC: L01XE14
CTHH: C26H29Cl2N5O3
PTK: 530.446
Bosutinib is a Bcr-Abl kinase inhibitor for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Compared to other tyrosine kinase inhibitors, it has a more favourable hematologic toxicity profile. FDA approved on September 4, 2012.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C26H29Cl2N5O3
Phân tử khối
530.446
Monoisotopic mass
529.164745233
InChI
InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
InChI Key
InChIKey=UBPYILGKFZZVDX-UHFFFAOYSA-N
IUPAC Name
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Traditional IUPAC Name
bosutinib
SMILES
COC1=CC(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C(Cl)C=C1Cl
Độ hòa tan
9.50e-03 g/l
logP
4.09
logS
-4.8
pKa (strongest acidic)
15.48
pKa (Strongest Basic)
8.43
PSA
82.88 Å2
Refractivity
142.12 m3·mol-1
Polarizability
56.14 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
8
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
MDDR-Like Rule
true
Cơ Chế Tác Dụng : Bosutinib is a Bcr-Abl kinase inhibitor for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Compared to other tyrosine kinase inhibitors, it has a more favourable hematologic toxicity profile. FDA approved on September 4, 2012. Bosutinib is a tyrosine kinase inhibitor. Although it is able to inhibit several tyrosine kinases such as Src, Lyn, and Hck, which are members of the Src-family of kinases, its primary target is the Bcr-Abl kinase. The Bcr-Abl gene is a chimeric oncogene created from the fusion of the breakpoint-cluster (Bcr) gene and Abelson (Abl) tyrosine gene. This chromosomal abnormality results in the formation of what is commonly known as the Philadelphia chromosome or Philadelphia translocation. The Bcr-Abl gene expresses a particular kinase that promotes the progression of CML. A decrease in the growth and size of the CML tumour has been observed following administration of bosutinib. Bosutinib did not inhibit the T315I and V299L mutant cells.
Dược Động Học :
▧ Absorption :
Food increase the exposure of bosutinib. Tmax, single dose, cancer patients, fed-state = 4-6 hours; After 15 daily doses of bosutinib 500 mg with food in CML patients, the pharmacokinetic parameters are as follows: Cmax = 200 ng/mL; AUC = 3650 ng∙h/mL
▧ Volume of Distribution :
Apparent volume of distribution = 6080 ± 1230 L.
▧ Protein binding :
94% bound to human plasma proteins in vitro. 96% bound to human plasma proteins in healthy subjects ex vivo. Extent of protein binding is not concentration-dependent.
▧ Metabolism :
Bosutinib is primarily metabolized by CYP3A4. The major circulating metabolites identified in plasma are oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite. All the metabolites were deemed inactive.
▧ Route of Elimination :
When given a single oral dose, 91.3% of the dose was recovered in feces and 3% of the dose recovered in urine.
▧ Half Life :
Terminal phase elimination half-life, single oral dose, fed-state = 22.5 hours
▧ Clearance :
Mean clearance (CL/F), single oral dose, fed-state = 189 L/h
Độc Tính : Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. Because bosutinib is not an inhibitor of c-KIT or PDGF receptor, it has less hematologic toxicities.
Chỉ Định : Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy in adult patients.
Tương Tác Thuốc :
  • Abiraterone Abiraterone increases levels by P-glycoprotein (MDR1) efflux transporter. Consider alternate therapy.
  • Crizotinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Digoxin Bosutinib is a substrate and inhibitor of p-glycoprotein (p-gp) and may increase levels of other p-gp substrates.
  • Etravirine Bosutinib, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid this combination.
  • Ketoconazole Strong CYP3A4 inhibitors may increase levels of bosutinib. Monitor concomitant therapy closely.
  • Lansoprazole Concomitant lansoprazole (PPI) decreased bosutinib Cmax by 46% and AUC by 26% compared to bosutinib alone. Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a reduction in bosutinib exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.
  • Rifampicin Strong CYP3A4 inducers may decrease levels of bosutinib. Monitor concomitant therapy closely.
Liều Lượng & Cách Dùng : Tablet - Oral - 100 mg, 500 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Bosulif
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06616
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03252
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0069-0136-01
Wikipedia
http://en.wikipedia.org/wiki/Bosutinib
RxList
http://www.rxlist.com/bosulif-drug.htm
Drugs.com
http://www.drugs.com/cdi/bosutinib.html
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