Tìm theo
Azacitidine
Các tên gọi khác (7 ) :
  • 4-Amino-1-beta-D-ribofuranosyl-S-triazin-2(1H)-one
  • 5 AZC
  • 5-Azacytidine
  • Azacitidina
  • Azacitidine
  • Azacitidinum
  • Azacytidine
enzyme inhibitors, antimetabolites antineoplastic
Thuốc Gốc
Small Molecule
CAS: 320-67-2
ĐG : Baxter International Inc. , http://www.baxter.com
CTHH: C8H12N4O5
PTK: 244.2047
A pyrimidine nucleoside analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C8H12N4O5
Phân tử khối
244.2047
Monoisotopic mass
244.080769514
InChI
InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1
InChI Key
InChIKey=NMUSYJAQQFHJEW-KVTDHHQDSA-N
IUPAC Name
4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one
Traditional IUPAC Name
azacitidine
SMILES
NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Độ tan chảy
229 °C
Độ hòa tan
8.9E+004 mg/L
logP
-3.5
logS
-1.3
pKa (strongest acidic)
12.55
pKa (Strongest Basic)
-0.38
PSA
140.97 Å2
Refractivity
52.19 m3·mol-1
Polarizability
21.5 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
8
H Bond Donor Count
4
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Dược Lực Học : Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. Upon uptake into cells, azacitidine is phosphorylated to 5-azacytidine monophosphate by uridine-cytidine kinase, then to diphosphate by pyrimidine monophosphate kinases and triphosphate by diphosphate kinases. 5-Azacitidine triphosphate is incorporated into RNA, leading to the disruption of nuclear and cytoplasmic RNA metabolism and inhibition of protein synthesis. 5-Azacytidine diphosphate is reduced to 5-aza-deoxycytidine diphosphate by ribonucleotide reductase. The resultant metabolite is phosphorylated to 5-azadeoxycitidine triphosphate by nucleoside diphosphate kinases. 5-azadeoxycitidine triphosphate is then incoporated into DNA, leading to inhibition of DNA synthesis. Azacitidine is most toxic during the S-phase of the cell cycle.
Cơ Chế Tác Dụng : A pyrimidine nucleoside analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. [PubChem] Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein. Its incorporation into DNA leads to a covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequent cytotoxicity.
Dược Động Học :
▧ Absorption :
Azacitidine is rapidly absorbed after subcutaneous administration. The bioavailability of subcutaneous azacitidine relative to IV azacitidine is approximately 89%, based on area under the curve.
▧ Volume of Distribution :
* 76 ± 26 L
▧ Metabolism :
An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine may be metabolized by the liver. The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known.
▧ Route of Elimination :
Following IV administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over three days. Mean excretion of radioactivity in urine following SC administration of 14C-azacitidine was 50%.
▧ Half Life :
Mean elimination half-life is approximately 4 hours.
▧ Clearance :
* 167 +/- 49 L/h
Độc Tính : One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.
Chỉ Định : For treatment of patients with the following French-American-British myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation (now classified as acute myelogenous leukemia with multilineage dysplasia), and chronic myelomonocytic leukemia.
Tương Tác Thuốc :
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng : Injection, powder, for solution - Subcutaneous
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Vidaza 100 mg vial
    Giá bán buôn : USD >588.23
    Đơn vị tính : vial
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Ladakamycin
  • Công ty :
    Sản phẩm biệt dược : Mylosar
  • Công ty :
    Sản phẩm biệt dược : Vidaza
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00928
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=9444
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46509032
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C11262
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03021
ChemSpider
http://www.chemspider.com/Chemical-Structure.9072.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67211-102-01
PharmGKB
http://www.pharmgkb.org/drug/PA451996
Wikipedia
http://en.wikipedia.org/wiki/Azacitidine
RxList
http://www.rxlist.com/cgi/generic3/vidaza.htm
Drugs.com
http://www.drugs.com/cdi/azacitidine.html
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