Tìm theo
Nilotinib
Các tên gọi khác (4 ) :
  • AMN 107
  • AMN-107
  • AMN107
  • Nilotinibum
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 641571-10-0
ATC: L01XE08
CTHH: C28H22F3N7O
PTK: 529.5158
Nilotinib, also known as AMN107, is a tyrosine kinase inhibitor under investigation as a possible treatment for chronic myelogenous leukemia (CML). In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib (Gleevec®), another tyrosine kinase inhibitor currently used as a first-line treatment. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C28H22F3N7O
Phân tử khối
529.5158
Monoisotopic mass
529.183792976
InChI
InChI=1S/C28H22F3N7O/c1-17-5-6-19(10-25(17)37-27-33-9-7-24(36-27)20-4-3-8-32-14-20)26(39)35-22-11-21(28(29,30)31)12-23(13-22)38-15-18(2)34-16-38/h3-16H,1-2H3,(H,35,39)(H,33,36,37)
InChI Key
InChIKey=HHZIURLSWUIHRB-UHFFFAOYSA-N
IUPAC Name
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzamide
Traditional IUPAC Name
nilotinib
SMILES
CC1=CN(C=N1)C1=CC(=CC(NC(=O)C2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)=C1)C(F)(F)F
Độ hòa tan
2.01e-03 g/l
logP
4.41
logS
-5.4
pKa (strongest acidic)
11.86
pKa (Strongest Basic)
6.3
PSA
97.62 Å2
Refractivity
152.85 m3·mol-1
Polarizability
52.35 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
5
Bioavailability
1
MDDR-Like Rule
true
Dược Lực Học : Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML).
Cơ Chế Tác Dụng : Nilotinib, also known as AMN107, is a tyrosine kinase inhibitor under investigation as a possible treatment for chronic myelogenous leukemia (CML). In June 2006, a Phase I clinical trial found nilotinib has a relatively favorable safety profile and shows activity in cases of CML resistant to treatment with imatinib (Gleevec®), another tyrosine kinase inhibitor currently used as a first-line treatment. [Wikipedia] Chronic myelogenous leukaemia (CML) is caused by the BCR-ABL oncogene. Nilotinib inhibits the tyrosine kinase activity of the BCR-ABL protein. Nilotinib fits into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib, over-riding resistance caused by mutations. The ability of AMN107 to inhibit TEL-platelet-derived growth factor receptor-beta (TEL-PDGFRbeta), which causes chronic myelomonocytic leukaemia, and FIP1-like-1-PDGFRalpha, which causes hypereosinophilic syndrome, suggests potential use of AMN107 for myeloproliferative diseases characterised by these kinase fusions (Stover et al, 2005; Weisberg et al, 2005). AMN107 also inhibits the c-Kit receptor kinase, including the D816V-mutated variant of KIT, at pharmacologically achievable concentrations, supporting potential utility in the treatment of mastocytosis, and gastrointestinal stromal tumours (Weisberg et al, 2005; von Bubnoff et al, 2005; Gleixner et al, 2006).
Dược Động Học :
▧ Absorption :
Orally available
▧ Half Life :
15 hours
Chỉ Định : For the potential treatment of various leukemias, including chronic myeloid leukemia (CML).
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Bendamustine P-glycoprotein (MDR-1) efflux transporter increases bendamustine levels.
  • Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Nilotinib prescribing information recommends avoiding concurrent use of nilotinib with strong inhibitors of CYP3A4.
  • Etravirine Nilotinib, when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Tacrolimus May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Tamoxifen Nilotinib may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Nilotinib, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Nilotinib is initiated, discontinued, or dose changed.
  • Telithromycin Telithromycin may reduce clearance of Nilotinib. Concomitant therapy should be avoided.
  • Thiothixene May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
  • Topotecan The p-glycoprotein inhibitor, Nilotinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Tramadol Nilotinib may decrease the effect of Tramadol by decreasing active metabolite production.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Tretinoin The moderate CYP2C8 inhibitor, Nilotinib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Nilotinib is initiated, discontinued to dose changed.
  • Trimipramine May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Voriconazole Voriconazole may increase the serum concentration of nilotinib by inhibiting its metabolism by CYP3A4. Additive QTc prolongation may also occur. Concomitant therapy should be avoided.
  • Vorinostat Additive QTc prolongation may occur. Concomitant therapy should be avoided.
  • Ziprasidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Zuclopenthixol Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided.
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Novartis
    Sản phẩm biệt dược : Tasigna
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04868
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=644241
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443226
ChemSpider
http://www.chemspider.com/Chemical-Structure.559260.html
PharmGKB
http://www.pharmgkb.org/drug/PA165958345
Wikipedia
http://en.wikipedia.org/wiki/Nilotinib
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