Synonym
Arranon, 506U78, GW506U78; GW-506U78; GW 506U78; Nelarabine; NSC-686673; NS-686673; NSC686673;
IUPAC/Chemical Name
(2R,3S,4R,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
InChi Key
IXOXBSCIXZEQEQ-XJCFNFQFSA-N
InChi Code
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
SMILES Code
O[C@@H]1[C@H](N2C=NC3=C(OC)N=C(N)N=C23)O[C@H](CO)[C@@H]1O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Nelarabine is an arabinonucleoside antimetabolite with antineoplastic activity. Nelarabine is demethoxylated by adenosine deaminase to become biologically active 9-beta-D-arabinosylguanine (ara-G); ara-G incorporates into DNA, thereby inhibiting DNA synthesis and inducing an S phase-dependent apoptosis of tumor cells. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
According to http://en.wikipedia.org/wiki/Nelarabine, Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. It was previously known as 506U78. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. Pre-clinical studies suggest that T-cells are particularly sensitive to nelarabine. In October 2005, it was approved by the FDA for T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma that has not responded to or has relapsed following treatment with at least two chemotherapy regimens. It was later approved in the European Union on August 22, 2007. Complete responses have been achieved with this medication. It is marketed in the US as Arranon and as Atriance in the EU by GlaxoSmithKline.
Drug Description
ARRANON (nelarabine) is a pro-drug of the cytotoxic deoxyguanosine analogue, 9-β-D-arabinofuranosylguanine (ara-G). The chemical name for nelarabine is 2-amino-9-β-D-arabinofuranosyl-6-methoxy-9H-purine. It has the molecular formula C11H15N5O5 and a molecular weight of 297.27. Nelarabine is slightly soluble to soluble in water and melts with decomposition between 209° and 217° C. ARRANON Injection is supplied as a clear, colorless, sterile solution in glass vials. Each vial contains 250 mg of nelarabine (5 mg nelarabine per mL) and the inactive ingredient sodium chloride (4.5 mg per mL) in 50 mL Water for Injection, USP. ARRANON is intended for intravenous infusion. Hydrochloric acid and sodium hydroxide may have been used to adjust the pH. The solution pH ranges from 5.0 to 7.0.
Mechanism of Action
Nelarabine is a pro-drug of the deoxyguanosine analogue 9-β-D-arabinofuranosylguanine (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G, mono-phosphorylated by deoxyguanosine kinase and deoxycytidine kinase, and subsequently converted to the active 5'-triphosphate, ara-GTP. Accumulation of ara-GTP in leukemic blasts allows for incorporation into deoxyribonucleic acid (DNA), leading to inhibition of DNA synthesis and cell death. Other mechanisms may contribute to the cytotoxic and systemic toxicity of nelarabine.
Biological target:
Nelarabine (506U78) is a nucleoside analogue.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
3.0 |
10.09 |
| DMSO |
49.9 |
167.97 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.68 |
| Water |
5.3 |
17.91 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
297.27
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
TBD
1: Commander LA, Seif AE, Insogna IG, Rheingold SR. Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma. Br J Haematol. 2010 May 26. [Epub ahead of print] PubMed PMID: 20528871.
2: Fullmer A, O'Brien S, Kantarjian H, Jabbour E. Novel therapies for relapsed acute lymphoblastic leukemia. Curr Hematol Malig Rep. 2009 Jul;4(3):148-56. PubMed PMID: 20425428.
3: Yamauchi T, Nishi R, Kitazumi K, Nakano T, Ueda T. A new high-performance liquid chromatography method determines low production of 9-beta-D-arabinofuranosylguanine triphosphate, an active metabolite of nelarabine, in adult T-cell leukemia cells. Oncol Rep. 2010 Feb;23(2):499-504. PubMed PMID: 20043113.
4: Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. Epub . PubMed PMID: 19828704; PubMed Central PMCID: PMC2792210.
5: 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. Review. PubMed PMID: 19825456.
6: Nelarabine: new drug. T-lymphoblastic leukaemia/lymphoma: more evaluation needed. Prescrire Int. 2009 Feb;18(99):3-5. PubMed PMID: 19382393.
7: Robak T, Korycka A, Lech-Maranda E, Robak P. Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules. 2009 Mar 23;14(3):1183-226. Review. PubMed PMID: 19325518.
8: Iino M. [Severe liver injury following nelarabine chemotherapy for T-cell lymphoblastic lymphoma]. Rinsho Ketsueki. 2009 Jan;50(1):49-51. Japanese. PubMed PMID: 19225230.
9: 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. Review. PubMed PMID: 19157550.
10: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 May;30(4):313-31. PubMed PMID: 18773127.
