Tìm theo
Tioguanine
Các tên gọi khác (21 ) :
  • 2-Amino 6mp
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-amino-1,9-Dihydropurine-6-thione
  • 2-amino-1H-purine-6(7H)-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-merkaptopurin
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-aminopurine-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6-Thioguanine
  • TG
  • ThG
  • Thioguanine
  • Tioguanin
  • Tioguanina
  • Tioguanine
  • Tioguaninum
antimetabolites antineoplastic
Thuốc Gốc
Small Molecule
CAS: 154-42-7
ATC: L01BB03
ĐG : DSM Corp. , http://www.dsm.com
CTHH: C5H5N5S
PTK: 167.192
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C5H5N5S
Phân tử khối
167.192
Monoisotopic mass
167.026565875
InChI
InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
InChI Key
InChIKey=WYWHKKSPHMUBEB-UHFFFAOYSA-N
IUPAC Name
2-amino-6,7-dihydro-3H-purine-6-thione
Traditional IUPAC Name
thioguanine
SMILES
NC1=NC(=S)C2=C(N1)N=CN2
Độ tan chảy
>360 °C
Độ hòa tan
36.3 mg/mL
logP
-0.07
logS
-2.3
pKa (strongest acidic)
10.53
pKa (Strongest Basic)
3.7
PSA
79.09 Å2
Refractivity
46.89 m3·mol-1
Polarizability
15.65 Å3
Rotatable Bond Count
0
H Bond Acceptor Count
4
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Dược Lực Học : Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase).
Cơ Chế Tác Dụng : An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem] Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides.
Dược Động Học :
▧ Absorption :
Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)
▧ Metabolism :
Hepatic. First converted to 6-thioguanilyic acid (TGMP). TGMP is further converted to the di- and tri-phosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP) by the same enzymes that metabolize guanine nucleotides.
▧ Half Life :
When the compound was given in singles doses of 65 to 300 mg/m^2, the median plasma half-disappearance time was 80 minutes (range 25-240 minutes)
Độc Tính : Oral, mouse: LD50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.
Chỉ Định : For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.
Tương Tác Thuốc :
  • Aminosalicylic Acid Aminosalicylic acid may increase the toxicity of thiopurine, thioguanine.
  • Busulfan Busulfan increases the hepatoxicity of Thioguanine during long-term concomitant therapy.
  • Mercaptopurine Complete cross resistance may occur.
  • Mesalazine Mesalazine may increase the toxicity of thiopurine, thioguanine.
  • Natalizumab The immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
  • Olsalazine Olsalazine may increase the toxicity of thiopurine, thioguanine.
  • Sulfasalazine Sulfasalazine may increase the toxicity of thiopurine, thioguanine.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng : Tablet - Oral - 40 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Lanvis
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Tabloid
  • Công ty : Induquimica
    Sản phẩm biệt dược : Tioguanina
  • Công ty : IFET
    Sản phẩm biệt dược : Tioguanine
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00352
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2723601
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508170
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07648
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06109
ChemSpider
http://www.chemspider.com/Chemical-Structure.2005804.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50200099
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0880-25
PharmGKB
http://www.pharmgkb.org/drug/PA451663
Wikipedia
http://en.wikipedia.org/wiki/Thioguanine
RxList
http://www.rxlist.com/cgi/generic2/thioguanine.htm
Drugs.com
http://www.drugs.com/cdi/thioguanine.html
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