Product Name: Nelarabine
Synonyms: (2R,3R,4S,5R)-2-(2-aMino-6-Methoxy-9H-purin-9-yl)-5-(hydroxyMethyl)-tetrahydrofuran-3,4-diol;Nelarabine (Arranon);506u;9-β-D-Arabinofuranosyl-6-Methoxy-9H-purin-2-aMine;Arranon;GW 506U78;MAY;(2R,3S,4S,5R)-2-(2-AMino-6-Methoxy-9H-purin-9-yl)-5-(hydroxyMethyl)tetrahydrofuran-3,4-diol
CAS: 121032-29-9
MF: C11H15N5O5
MW: 297.27
EINECS: 642-916-9
Product Categories: Heterocycles;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;5g,10g,25g,100g;ARRANON;Bases & Related Reagents;Anti-cancer&immunity;API;Inhibitors
Mol File: 121032-29-9.mol

Nelarabine Chemical Properties
Melting point  209-217°
alpha  D20 +55.9° (c = 0.27 in DMF)
Boiling point  721.0±70.0 °C(Predicted)
density  1.98±0.1 g/cm3(Predicted)
pka 13.07±0.70(Predicted)
CAS DataBase Reference 121032-29-9(CAS DataBase Reference)

Physical properties White or almost white crystalline powder. This product is slightly soluble in water, the solubility in water is about 8-9mg/ml (25 ℃, PH = 4~10).
Developed by GlaxoSmithKline Nelarabine is a prodrug for deoxyguanosine analogue ——9-beta-D-arabinofuranosyl guanine (ara-G). Nelarabine demethylates in the role of adenosine deaminase (ADA) and turns into ara-G. Then, It turns into active ara-G triphosphate (ara-GTP) in the role of the deoxyguanosine kinase and deoxycytidine kinase and under the action of the monophosphorylation pathway. Ara-GTP can accumulate in leukemia cells, and bind to DNA to inhibit DNA synthesis, and accelerate leukemia cell death. In addition, the anti-cancer mechanism of Nelarabine may also be related to its cytotoxicity and somatic toxicity.
Nelarabine was first successfully developed by GlaxoSmithKline. On October 28, 2005 under the approval of the US Food and Drug Administration, it became a new drug for curing T-cell acute lymphoblastic leukemia (T-ALL) and T-Cells lymphoblasticlymphoma (T-LBL) which are resistant to at least two types of chemotherapy regimens or relapsed after initial treatment. This new drug officially listed in the United States in 2006. This product didn’t apply for patent and administrative protection in China, so the development of this product does not exist intellectual property issues.
Pharmacology and pharmacokinetics Nelarabine is a prodrug for deoxyguanosine analogue 9-β-arabinosyl guanine (ara-G). Ara-G has poor water solubility and can become Nelarabine with methoxy group in vivo. It was mono-phosphorylated into 5'-triphosphate ara-G, when catalyzed by adenosine deaminase and deoxycytidine kinase. Ara cells-GTP is accumulated in leukemia. PNP deficiency leads to the selective accumulation of dGTP in T cells, whereas dGTP rapidly degrades in B cells without accumulation in B cells. Intracellular accumulation of dGTP can inhibit DNA synthesis. Arabinosyl guanine can selectively kill cells with T cell leukemia, leading to cell death. Other mechanisms may be cytotoxicity and systemic toxicity of Nelarabine.
Recurrent pharmacokinetic study of leukemia or lymphoma in patients found that Nelarabine and ara-G can eliminated in plasma quickly. the two half-life were 30 minutes and 3 hour when giving 1500mg/m2 dose of Nelarabine. The study also found that ara-G usually reached the peak concentration at the end of Nelarabine administration, and its peak concentration value is usually greater than the peak concentration of Nelarabine, indicating that Nelarabine in the body can be quickly and completely transformed into ara-G. Nelarabine and ara-G were partially abolished by the kidneys, and the mean renal excretion rates of Nelarabine and ara-G measured 24 hours after administration of Nelarabine in 28 adult patients were 6.6 ± 4.7% and 27 ± 15% .

Physical properties White or almost white crystalline powder. This product is slightly soluble in water, the solubility in water is about 8-9mg/ml (25 ℃, PH = 4~10).
Developed by GlaxoSmithKline Nelarabine is a prodrug for deoxyguanosine analogue ——9-beta-D-arabinofuranosyl guanine (ara-G). Nelarabine demethylates in the role of adenosine deaminase (ADA) and turns into ara-G. Then, It turns into active ara-G triphosphate (ara-GTP) in the role of the deoxyguanosine kinase and deoxycytidine kinase and under the action of the monophosphorylation pathway. Ara-GTP can accumulate in leukemia cells, and bind to DNA to inhibit DNA synthesis, and accelerate leukemia cell death. In addition, the anti-cancer mechanism of Nelarabine may also be related to its cytotoxicity and somatic toxicity.
Nelarabine was first successfully developed by GlaxoSmithKline. On October 28, 2005 under the approval of the US Food and Drug Administration, it became a new drug for curing T-cell acute lymphoblastic leukemia (T-ALL) and T-Cells lymphoblasticlymphoma (T-LBL) which are resistant to at least two types of chemotherapy regimens or relapsed after initial treatment. This new drug officially listed in the United States in 2006. This product didn’t apply for patent and administrative protection in China, so the development of this product does not exist intellectual property issues.
Pharmacology and pharmacokinetics Nelarabine is a prodrug for deoxyguanosine analogue 9-β-arabinosyl guanine (ara-G). Ara-G has poor water solubility and can become Nelarabine with methoxy group in vivo. It was mono-phosphorylated into 5'-triphosphate ara-G, when catalyzed by adenosine deaminase and deoxycytidine kinase. Ara cells-GTP is accumulated in leukemia. PNP deficiency leads to the selective accumulation of dGTP in T cells, whereas dGTP rapidly degrades in B cells without accumulation in B cells. Intracellular accumulation of dGTP can inhibit DNA synthesis. Arabinosyl guanine can selectively kill cells with T cell leukemia, leading to cell death. Other mechanisms may be cytotoxicity and systemic toxicity of Nelarabine.
Recurrent pharmacokinetic study of leukemia or lymphoma in patients found that Nelarabine and ara-G can eliminated in plasma quickly. the two half-life were 30 minutes and 3 hour when giving 1500mg/m2 dose of Nelarabine. The study also found that ara-G usually reached the peak concentration at the end of Nelarabine administration, and its peak concentration value is usually greater than the peak concentration of Nelarabine, indicating that Nelarabine in the body can be quickly and completely transformed into ara-G. Nelarabine and ara-G were partially abolished by the kidneys, and the mean renal excretion rates of Nelarabine and ara-G measured 24 hours after administration of Nelarabine in 28 adult patients were 6.6 ± 4.7% and 27 ± 15% .