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Nelarabine

产品号 DB01280 公司名称 DrugBank
CAS号 121032-29-9 公司网站 http://www.ualberta.ca/
分子式 C11H15N5O5 电 话 (780) 492-3111
分子量 297.2673 传 真
纯 度 电子邮件 david.wishart@ualberta.ca
保 存 Chembase数据库ID: 1139

产品价格信息

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产品别名

标题
Nelarabine
IUPAC标准名
(2R,3S,4S,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
IUPAC传统名
nelarabine
商标名
Arranon
Arranon (GlaxoSmithKline)
Atriance
别名
Nelzarabine
GW-506U78
nelarabine

产品登记号

PubChem CID 3011155
CAS号 121032-29-9
PubChem SID 46506325

产品性质

疏水性(logP) -1
溶解度 Slightly soluble to soluble in water

产品详细信息

详细说明 (English)
Item Information
Drug Groups approved; investigational
Description 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.
Indication 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.
Pharmacology 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.
Toxicity 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.
Affected Organisms
Humans and other mammals
Biotransformation 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.
Half Life Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.
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.
Elimination Excretion: Nelarabine and ara-G are partially eliminated by the kidneys.
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]
References
Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Pubmed]
DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. [Pubmed]
Roecker AM, Allison JC, Kisor DF: Nelarabine: efficacy in the treatment of clinical malignancies. Future Oncol. 2006 Aug;2(4):441-8. [Pubmed]
Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. [Pubmed]
Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Pubmed]
Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Pubmed]
Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Pubmed]
Sigalas P, Tourvas AD, Moulakakis A, Pangalis G, Kontopidou F: Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature. Leuk Res. 2009 Jul;33(7):e61-3. Epub 2009 Jan 21. [Pubmed]
Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com

参考文献

  • Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. Pubmed
  • Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. Pubmed
  • Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. Pubmed
  • Sigalas P, Tourvas AD, Moulakakis A, Pangalis G, Kontopidou F: Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature. Leuk Res. 2009 Jul;33(7):e61-3. Epub 2009 Jan 21. Pubmed
  • Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. Pubmed
  • DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. Pubmed
  • Roecker AM, Allison JC, Kisor DF: Nelarabine: efficacy in the treatment of clinical malignancies. Future Oncol. 2006 Aug;2(4):441-8. Pubmed
  • Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. Pubmed
  • Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. Pubmed