Nelarabine

• Catalog No.: S1213
• CAS Number: 121032-29-9
• M. F.: C11H15N5O5
• M. W.: 297.2673
• Storage: -20°C

SYNONYMS

• IUPAC name: (2R,3S,4S,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• IUPAC Traditional name: (2R,3S,4S,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• Synonyms: Arranon

DATABASE IDS

• CAS Number: 121032-29-9

PROPERTIES

• Target: DNA/RNA synthesis
• Salt Data: Free Base
• Solubility: DMSO
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cancer

Biological Activity

• Description: Nelarabine (Arranon, 506U78) is a purine nucleoside analog and DNA synthesis inhibitor for HSB2 cell lines and ALL-SIL cell lines with IC50 of 0.13 μg/mL and 0.37 μg/mL, respectively.
• Targets: HSB2 cell lines; ALL-SIL cell lines; JURKAT cell lines; PER-255 cell lines
• IC50: 0.13 μg/mL; 0.37 μg/mL; 0.64 μg/mL; 0.02 μg/mL ^[1]
• In Vitro: The IC50 of Nelarabine is 25-fold and 113-fold higher than ARAC in T- and B-lineage, respectively. T-ALL cells are eightfold more sensitive to Nelarabine than B-lineage but there is considerable overlap. The efficacy of NEL in T-lineage and B-lineage cell lines is 25-fold and 113-fold less than ARAC, respectively. ^[1] Nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in susceptible cells. ^[2]Nelarabine demonstrated significant antineoplastic activity with acceptable toxicity. ^[3]
• In Vivo: The Nelarabine plasma AUC is 2.82 mM minutes and the ara-G plasma AUC is 20 mM minutes. The terminal half-life of Nelarabine in plasma is 25 min, clearance is 42 mL/minutes/kg, and central volume of distribution is 1.1 L/kg. The terminal half-life of ara-G in plasma is 182 minutes and the central volume of distribution is 1.4 L/kg. In CSF the terminal half-life of Nelarabine is 77 minutes and of ara-G is 232 minutes. The AUCcsf:AUCplasma is 29 % for Nelarabine and 23 % for ara-G. Nelarabine and ara-G do not accumulate with daily infusions because of their relatively short half-lives. ^[4]
• Clinical Trials: Nelarabine plus Doxorubicin, Cyclophosphamide,Cytarabine, Dexamethasone, Methotrexate or Vincristine has entered in a phase II clinical trial in the treatment of leukemia, acute lymphoblastic leukemia, and lymphoblastic lymphoma.
• Features: Nelarabine is rapidly converted into ara-G through demethoxylation by adenosine deaminase.

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: HSB2, ALL-SIL, JURKAT and PER-255 cell lines
• Concentrations: 0.125 μg/mL - 8 μg/mL
• Incubation Time: 96 hours
• Methods: HSB2, ALL-SIL, JURKAT and PER-255 cell lines are tested for drug resistance using the MTT assay. Nelarabine are incubated over 4 days, with concentration tested in triplicate. The IC50 (drug concentration that inhibits cell growth by 50%) is used as the measure of drug resistance. Data represent the average of 2–6 experiments performed on separate occasions. In cases where 50% cytotoxicity is not achieved by even the highest dose in a particular experiment, the IC50 is recorded as double the highest concentration tested.
• Protocol: Animal Study ^[4]
• Animal Models: Healthy adult male rhesus monkeys
• Formulation: Control
• Doses: 35 mg/kg
• Administration: Administered via i.v.

References

• References: [1] Beesley AH, et al. Br J Haematol. 2007, 137(2), 109-116.
• References: [2] Kline J, et al. Expert Opin Pharmacother. 2006, 7(13), 1791-1799.
• References: [3] DeAngelo DJ, et al. Blood. 2007, 109(12), 5136-5142.
• References: [4] Berg SL, et al. Cancer Chemother Pharmacol. 2007, 59(6), 743-747.

REFERENCES

• Berg SL, et al. Cancer Chemother Pharmacol. 2007, 59(6), 743-747.
• DeAngelo DJ, et al. Blood. 2007, 109(12), 5136-5142.
• Beesley AH, et al. Br J Haematol. 2007, 137(2), 109-116.
• Kline J, et al. Expert Opin Pharmacother. 2006, 7(13), 1791-1799.