Tìm theo
Imatinib
Các tên gọi khác (6 ) :
  • 4-(4-METHYL-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide
  • alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-P-toluidide
  • Imatinib
  • Imatinib Methansulfonate
  • Imatinibum
  • STI 571
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 152459-95-5
ATC: L01XE01
ĐG : Murfreesboro Pharmaceutical Nursing Supply , http://www.unitdosesupply.com
CTHH: C29H31N7O
PTK: 493.6027
Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H31N7O
Phân tử khối
493.6027
Monoisotopic mass
493.259008649
InChI
InChI=1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)
InChI Key
InChIKey=KTUFNOKKBVMGRW-UHFFFAOYSA-N
IUPAC Name
N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide
Traditional IUPAC Name
imatinib
SMILES
CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1
Độ tan chảy
226 °C (mesylate salt)
Độ hòa tan
Very soluble in water at pH < 5.5 (mesylate salt)
logP
3
logS
-4.5
pKa (strongest acidic)
12.45
pKa (Strongest Basic)
8.27
PSA
86.28 Å2
Refractivity
148.93 m3·mol-1
Polarizability
55.54 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
7
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Imatinib is an antineoplastic agent used to treat chronic myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of Abl with Bcr (breakpoint cluster region), termed Bcr-Abl. As this is now a continuously active tyrosine kinase, Imatinib is used to decrease Bcr-Abl activity.
Cơ Chế Tác Dụng : Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells. Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib also inhibits the receptor tyrosine kinases for platelet derived growth factor (PDGF) and stem cell factor (SCF) - called c-kit. Imatinib was identified in the late 1990s by Dr Brian J. Druker. Its development is an excellent example of rational drug design. Soon after identification of the bcr-abl target, the search for an inhibitor began. Chemists used a high-throughput screen of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.
Dược Động Học :
▧ Absorption :
The pharmacokinetics in CML and GIST patients are similar. Imatinib is well absorbed with mean absolute bioavailability is 98% and maximum plasma levels achieved within 2-4 hours of dosing
▧ Protein binding :
95% protein bound, mostly to albumin and alpha-1-acid glycoprotein.
▧ Metabolism :
Primarily hepatic via CYP3A4. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. This metabolite is similar in potency to the parent compound.
▧ Route of Elimination :
Imatinib elimination is predominately in the feces, mostly as metabolites. 81% of the dose is eliminated within 7 days, in feces (68% of the dose) and urine (13% of the dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faces), the remainder being metabolites.
▧ Half Life :
Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-demethyl derivative (CGP74588) are approximately 18 and 40 hours, respectively.
▧ Clearance :
* 8 L/h [50-year-old CML and GIST patient weighing 50 kg] * 14 L/h [50-year-old CML and GIST patient weighing 100 kg]
Độc Tính : The most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.
Chỉ Định : For the treatment of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), Ph+ acute lymphoblastic leukaemia, myelodysplastic/myeloproliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST).
Tương Tác Thuốc :
  • Acenocoumarol Imatinib may increase the anticoagulant effect of acenocoumarol.
  • Acetaminophen Increased hepatic toxicity of both agents
  • Anisindione Imatinib may increase the anticoagulant effect of anisindione.
  • Aprepitant Aprepitant may change levels of the chemotherapy agent, imatinib.
  • Atorvastatin Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if imatinib is initiated, discontinued or dose changed.
  • Bromazepam Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if imatinib is initiated, discontinued or dose changed. Dosage adjustments may be required.
  • Carbamazepine Carbamazepine, a strong CYP3A4 inducer, may increase the metabolism of imatinib. Imatinib, a strong CYP3A4 inhibitor, may increase the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.
  • Cerivastatin Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if imatinib is initiated, discontinued or dose changed.
  • Clarithromycin The macrolide, clarithromycin, may increase the serum concentration of imatinib.
  • Cyclosporine Imatinib increases the effect and toxicity of cyclosporine
  • Dantrolene Imatinib may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if imatinib is initiated, discontinued or dose changed.
  • Dexamethasone Dexamethasone may decrease levels of imatinib.
  • Dicoumarol Imatinib may increase the anticoagulant effect of dicumarol.
  • Erythromycin The macrolide, erythromycin, may increase the serum concentration of imatinib.
  • Ethotoin The hydantoin decreases the levels of imatinib
  • Etravirine Imatinib, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid this combination if alternative are available. If concurrent use is not avoidable, it is recommended to increase the dosage of cabozantinib by a minimum of 50%, and to monitor therapy.
  • Fosphenytoin The hydantoin decreases the levels of imatinib
  • Itraconazole Itraconazole may increase the levels of imatinib.
  • Josamycin The macrolide, josamycin, may increase the serum concentration of imatinib.
  • Ketoconazole Ketoconazole may increase the levels of imatinib.
  • Lovastatin Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if imatinib is initiated, discontinued or dose changed.
  • Lurasidone Concomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
  • Mephenytoin The hydantoin decreases the levels of imatinib
  • Nifedipine Imatinib increases the effect and toxicity of nifedipine
  • Phenobarbital Phenobarbital decreases levels of imatinib
  • Phenytoin The hydantoin decreases the levels of imatinib
  • Pimozide Imatinib may increase the effect and toxicity of pimozide.
  • Rifampicin Rifampin decreases levels of imatinib
  • Simvastatin Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if imatinib is initiated, discontinued or dose changed.
  • St. John's Wort St. John's Wort decreases levels of imatinib
  • Tacrolimus The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Imatinib is initiated, discontinued or dose changed.
  • Tadalafil Imatinib may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Imatinib may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Imatinib may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Imatinib is initiated, discontinued or dose changed.
  • Tamsulosin Imatinib, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imatinib is initiated, discontinued, or dose changed.
  • Telithromycin Co-administration may result in altered plasma concentrations of Imatinib and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
  • Temsirolimus Imatinib may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Imatinib is initiated, discontinued or dose changed.
  • Tiagabine The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Imatinib is initiated, discontinued or dose changed.
  • Tolterodine Imatinib may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The BCRP/ABCG2 inhibitor, Imatinib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Imatinib is initiated, discontinued or dose changed.
  • Tramadol Imatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Imatinib 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.
  • Trazodone The CYP3A4 inhibitor, Imatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Imatinib is initiated, discontinued or dose changed.
  • Trimipramine The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Imatinib is initiated, discontinued or dose changed.
  • Vardenafil Imatinib, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
  • Venlafaxine Imatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Imatinib is initiated, discontinued, or dose changed.
  • Verapamil Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Imatinib is initiated, discontinued or dose changed.
  • Vinblastine Imatinib, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Imatinib is initiated, discontinued or dose changed.
  • Vincristine Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Imatinib is initiated, discontinued or dose changed.
  • Vinorelbine Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Imatinib is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of imatinib by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of imatinib if voriconazole is initiated, discontinued or dose changed.
  • Warfarin Imatinib may increase the anticoagulant effect of warfarin increasing the risk of bleeding. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if imatinib is initiated, discontinued or dose changed.
  • Zonisamide Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if imatinib is initiated, discontinued or dose changed.
  • Zopiclone Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if imatinib is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 100 mg, 400 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Gleevec 100 mg tablet
    Giá bán buôn : USD >41.69
    Đơn vị tính : tablet
  • Biệt dược thương mại : Gleevec 400 mg tablet
    Giá bán buôn : USD >174.38
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Celon
    Sản phẩm biệt dược : Celonib
  • Công ty : Orion
    Sản phẩm biệt dược : Enliven
  • Công ty : Novartis
    Sản phẩm biệt dược : Gleevec
  • Công ty : Novartis
    Sản phẩm biệt dược : Glivec
  • Công ty : Grey Inversiones
    Sản phẩm biệt dược : Imatib
  • Công ty : Miracalus
    Sản phẩm biệt dược : Mesylonib
  • Công ty : Glenmark
    Sản phẩm biệt dược : Mitinab
  • Công ty : Pliva
    Sản phẩm biệt dược : Plivatinib
  • Công ty : Shantha
    Sản phẩm biệt dược : Shantinib
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00619
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5291
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505055
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01441
ChemSpider
http://www.chemspider.com/Chemical-Structure.5101.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=13530
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0401-34
PharmGKB
http://www.pharmgkb.org/drug/PA10804
Wikipedia
http://en.wikipedia.org/wiki/Imatinib
RxList
http://www.rxlist.com/cgi/generic3/gleevec.htm
Drugs.com
http://www.drugs.com/cdi/imatinib.html
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