Tìm theo
Nelarabine
Các tên gọi khác (4 ) :
  • 2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine
  • Arranon
  • GW-506U78
  • Nelzarabine
Thuốc Gốc
Small Molecule
CAS: 121032-29-9
ATC: L01BB07
ĐG : GlaxoSmithKline Inc. , http://www.gsk.com
CTHH: C11H15N5O5
PTK: 297.2673
Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C11H15N5O5
Phân tử khối
297.2673
Monoisotopic mass
297.107318615
InChI
InChI=1S/C11H15N5O5/c1-20-9-5-8(14-11(12)15-9)16(3-13-5)10-7(19)6(18)4(2-17)21-10/h3-4,6-7,10,17-19H,2H2,1H3,(H2,12,14,15)/t4-,6-,7+,10-/m1/s1
InChI Key
InChIKey=IXOXBSCIXZEQEQ-UHTZMRCNSA-N
IUPAC Name
(2R,3S,4S,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
Traditional IUPAC Name
nelarabine
SMILES
COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Độ tan chảy
209-217 °C (with decomposition)
Độ hòa tan
Slightly soluble to soluble in water
logP
-1
logS
-1.3
pKa (strongest acidic)
12.45
pKa (Strongest Basic)
3.47
PSA
148.77 Å2
Refractivity
69.6 m3·mol-1
Polarizability
27.68 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
9
H Bond Donor Count
4
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Dược Lực Học : Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies suggest that T-cells are particularly sensitive to nelarabine.
Cơ Chế Tác Dụng : Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.
Dược Động Học :

▧ Protein binding :
Nelarabine and ara-G are not substantially bound to human plasma proteins (<25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 mM.
▧ Metabolism :
The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolyzed to form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid. Ring opening of uric acid followed by further oxidation results in the formation of allantoin.
▧ Route of Elimination :
Excretion: Nelarabine and ara-G are partially eliminated by the kidneys.
▧ Half Life :
Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.
▧ Clearance :
* 197  +/-  189 L/h/m2 [Adult patients with refractory leukemia or lymphoma receiving doses of 199 to 2,900 mg/m2] * 259  +/-  409 L/h/m2 [Pediatric patients with refractory leukemia or lymphoma receiving doses of 104 to 2,900 mg/m2]
Độc Tính : A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death.
Chỉ Định : For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.
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, solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Arranon 250 mg vial
    Giá bán buôn : USD >12.75
    Đơn vị tính : ml
Nhà Sản Xuất
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Arranon
  • Công ty :
    Sản phẩm biệt dược : Atriance
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01280
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3011155
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506325
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D05134
ChemSpider
http://www.chemspider.com/Chemical-Structure.2280207.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0007-4401-06
PharmGKB
http://www.pharmgkb.org/drug/PA164752425
Wikipedia
http://en.wikipedia.org/wiki/Nelarabine
RxList
http://www.rxlist.com/cgi/generic/arranon.htm
Drugs.com
http://www.drugs.com/cdi/nelarabine.html
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