Tìm theo
Decitabine
Các tên gọi khác (6 ) :
  • 4-amino-1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-S-triazin-2(1H)-one
  • 5-aza-2'-deoxycytidine
  • 5-Azadeoxycytidine
  • Azadc
  • Decitabine
  • Dezocitidine
enzyme inhibitors, antimetabolites antineoplastic, teratogens
Thuốc Gốc
Small Molecule
CAS: 2353-33-5
ĐG : Eisai Inc. , http://www.eisai.com
CTHH: C8H12N4O4
PTK: 228.2053
Decitabine is indicated for treatment of patients with myelodysplastic syndrome (MDS). It is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Cells in the presence of Decitabine incorporate it into DNA during replication and RNA during transcription. The incorporation of Decitabine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence. This adversely affects the way that cell regulatory proteins are able to bind to the DNA/RNA substrate.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C8H12N4O4
Phân tử khối
228.2053
Monoisotopic mass
228.085854892
InChI
InChI=1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1
InChI Key
InChIKey=XAUDJQYHKZQPEU-KVQBGUIXSA-N
IUPAC Name
4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one
Traditional IUPAC Name
decitabine
SMILES
NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
Độ hòa tan
Sparingly soluble
logP
-2.2
logS
-1.6
pKa (strongest acidic)
13.89
pKa (Strongest Basic)
-0.25
PSA
120.74 Å2
Refractivity
50.68 m3·mol-1
Polarizability
21.15 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
7
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Dược Lực Học : Decitabine is an analogue of the natural nucleoside 2’-deoxycytidine. It functions in the same way as 5-Azacytidine. The antineoplastic activity of this drug is dependent on its intracellular conversion to its 5'-triphosphate metabolite.
Cơ Chế Tác Dụng : Decitabine is indicated for treatment of patients with myelodysplastic syndrome (MDS). It is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Cells in the presence of Decitabine incorporate it into DNA during replication and RNA during transcription. The incorporation of Decitabine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence. This adversely affects the way that cell regulatory proteins are able to bind to the DNA/RNA substrate. Decitabine is believed to exert its antineoplastic effects following its conversion to decitabine triphosphate, where the drug directly incorporates into DNA and inhibits DNA methyltransferase, the enzyme that is responsible for methylating newly synthesized DNA in mammalian cells. This results in hypomethylation of DNA and cellular differentiation or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine that has been incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine. Decitabine is cell cycle specific and acts peripherally in the S phase of the cell cycle. It does not inhibit the progression of cells from the G1 to S phase.
Dược Động Học :

▧ Protein binding :
Plasma protein binding of decitabine is negligible (<1%).
▧ Metabolism :
The exact route of elimination and metabolic fate of decitabine is not known in humans. One of the pathways of elimination of decitabine appears to be deamination by cytidine deaminase found principally in the liver but also in granulocytes, intestinal epithelium and whole blood.
▧ Half Life :
The terminal phase elimination half-life is 0.51 ± 0.31 hours.
▧ Clearance :
* 125 L/h/m2 [Patients receiving 15 mg/m2 3-hr infusion every 8 hours for 3 days] * 210 L/h/m2 [20 mg/m2 1-hr infusion daily for 5 days]
Độc Tính : There is no known antidote for overdosage with decitabine. Higher doses are associated with increased myelosuppression including prolonged neutropenia and thrombocytopenia.
Chỉ Định : For treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups (scores ≥0.5).
Liều Lượng & Cách Dùng : Powder, for solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Dacogen 50 mg vial
    Giá bán buôn : USD >1706.4
    Đơn vị tính : vial
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Dacogen
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01262
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=451668
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505657
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03665
ChemSpider
http://www.chemspider.com/Chemical-Structure.397844.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/62856-600-01
PharmGKB
http://www.pharmgkb.org/drug/PA164749631
Wikipedia
http://en.wikipedia.org/wiki/Decitabine
Drugs.com
http://www.drugs.com/cdi/decitabine.html
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