Tìm theo
Erlotinib
Các tên gọi khác (3) :
  • [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine
  • Erlotinib
  • OSI-774
protein kinase inhibitors
Thuốc Gốc
Small Molecule
CAS: 183321-74-6
ATC: L01XE03
ĐG : F Hoffmann-La Roche Ltd. , http://www.roche.com
CTHH: C22H23N3O4
PTK: 393.4357
Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H23N3O4
Phân tử khối
393.4357
Monoisotopic mass
393.168856239
InChI
InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
InChI Key
InChIKey=AAKJLRGGTJKAMG-UHFFFAOYSA-N
IUPAC Name
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
Traditional IUPAC Name
erlotinib
SMILES
COCCOC1=C(OCCOC)C=C2C(NC3=CC=CC(=C3)C#C)=NC=NC2=C1
Độ hòa tan
Very slightly soluble (hydrochloride salt - maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2)
logP
2.7
logS
-4.6
pKa (strongest acidic)
16.14
pKa (Strongest Basic)
4.59
PSA
74.73 Å2
Refractivity
107.79 m3·mol-1
Polarizability
43.48 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
7
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Cơ Chế Tác Dụng : Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders. The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.
Dược Động Học :
▧ Absorption :
Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Solubility decreases pH increases. Smoking also decrease the exposure of erlotinib.
▧ Volume of Distribution :
Apparent volume of distribution = 232 L
▧ Protein binding :
93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)
▧ Metabolism :
Metabolism occurs in the liver. In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.
▧ Route of Elimination :
Following a 100 mg oral dose, 91% of the dose was recovered in which 83% was in feces (1% of the dose as unchanged parent compound) and 8% in urine (0.3% of the dose as unchanged parent compound).
▧ Half Life :
Median half-life of 36.2 hours.
▧ Clearance :
Smokers have a 24% higher rate of erlotinib clearance.
Độc Tính : Symptoms of overdose include diarrhea, rash, and liver transaminase elevation. The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia.
Chỉ Định : For the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
Tương Tác Thuốc :
  • Atazanavir This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Clarithromycin This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Erythromycin This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Indinavir This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Itraconazole Itraconazole may decrease the metabolism of erlotinib. Monitor for changes in the therapeutic and adverse effects of erlotinib if itraconazole is initiated, discontinued or dose changed.
  • Ketoconazole This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Nefazodone This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Nelfinavir This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Rifabutin Decreased levels/effect of erlotinib
  • Rifampicin Decreased levels/effect of erlotinib
  • Rifapentine Decreased levels/effect of erlotinib
  • Ritonavir This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Saquinavir This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • St. John's Wort Decreased levels/effect of erlotinib
  • Telithromycin Telithromycin may reduce clearance of Erlotinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Erlotinib if Telithromycin is initiated, discontinued or dose changed.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Troleandomycin This CYP3A4 inhibitor increases levels/toxicity of erlotinib
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of erlotinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of erlotinib if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 25 mg, 100 mg, 150 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Tarceva 25 mg tablet
    Giá bán buôn : USD >52.78
    Đơn vị tính : tablet
  • Biệt dược thương mại : Tarceva 100 mg tablet
    Giá bán buôn : USD >144.98
    Đơn vị tính : tablet
  • Biệt dược thương mại : Tarceva 150 mg tablet
    Giá bán buôn : USD >163.98
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Genetech
    Sản phẩm biệt dược : Tarceva
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00530
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=176870
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508021
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07907
ChemSpider
http://www.chemspider.com/Chemical-Structure.154044.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=5446
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/54868-5447-0
PharmGKB
http://www.pharmgkb.org/drug/PA134687924
Wikipedia
http://en.wikipedia.org/wiki/Erlotinib
RxList
http://www.rxlist.com/cgi/generic4/tarceva.htm
Drugs.com
http://www.drugs.com/cdi/erlotinib.html
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