Repositioning Candidate Details
| Candidate ID: | R0477 |
| Source ID: | DB01280 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Nelarabine |
| Synonyms: | 2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine; Nelarabine; Nelzarabine |
| Molecular Formula: | C11H15N5O5 |
| SMILES: | COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O |
| Structure: |
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| DrugBank Description: | Nelarabine is an antineoplastic agent that is typically employed to treat acute T-cell lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. |
| CAS Number: | 121032-29-9 |
| Molecular Weight: | 297.2673 |
| DrugBank 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. |
| DrugBank 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 have demonstrated that targeted T-cells possess marked sensitivity to the agent. |
| DrugBank MoA: | Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood. |
| Targets: | DNA incorporation into and destabilization; DNA polymerase alpha catalytic subunit inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
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