product name Nelarabine
Description: Nelarabine (also known as 506U78) is a purine nucleoside analog and DNA synthesis inhibitor with IC50 from 0.067-2.15 μM in tumor cells. It acts as an inhibitor by inhibiting DNA synthesis and as an inducer by inducing apoptosis in malignant cells. Nelarabine requires demethylation by adenosine deaminase (ADA) in plasma to form the active compound, ara-G. Intracellular by deoxyguanosine kinase and deoxycytidine kinase phosphorylate ara-G to its triphosphate form, ara-GTP. Inside the cell exposure to ara-GTP is much higher than the exposure to ara-G or nelarabine.
References: Br J Haematol. 2007 Apr;137(2):109-16; Expert Opin Pharmacother. 2006 Sep;7(13):1791-9; Cancer Chemother Pharmacol. 2007 May;59(6):743-7.
297.27
Formula
C11H15N5O5
CAS No.
121032-29-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 60 mg/mL (201.8 mM)
Water: 3 mg/mL (10.1 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
506U78
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19412830
| In Vitro |
In vitro activity: 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. Nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in susceptible cells. Nelarabine demonstrated significant antineoplastic activity with acceptable toxicity. Kinase Assay: Cell Assay: 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. |
|---|---|
| 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. |
| Animal model | Healthy adult male rhesus monkeys |
| Formulation & Dosage | 35 mg/kg; i.v. injection |
| References | Br J Haematol. 2007 Apr;137(2):109-16; Expert Opin Pharmacother. 2006 Sep;7(13):1791-9; Cancer Chemother Pharmacol. 2007 May;59(6):743-7. |
