Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C11H15N5O5 |
Molecular Weight | 297.2673 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=NC(N)=NC2=C1N=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3O
InChI
InChIKey=IXOXBSCIXZEQEQ-UHTZMRCNSA-N
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
Molecular Formula | C11H15N5O5 |
Molecular Weight | 297.2673 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Arranon is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. It is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. Administration of nelarabine in combination with adenosine deaminase inhibitors, such 195 as pentostatin, is not recommended. The most common (≥20%) adverse reactions were: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/18318562
Curator's Comment: Nelarabine is widely distributed throughout the body and lower levels detected in the CNS
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18318562 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ARRANON Approved UseARRANON is indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted. ARRANON is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted. (1) Launch Date2005 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5 μg/mL |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.4 μg × h/mL |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.5 h |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
16.5 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10694549 |
75 mg/kg 2 times / hour multiple, intravenous dose: 75 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
NELARABINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2900 mg/m2 3 times / 3 weeks multiple, intravenous Highest studied dose Dose: 2900 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 2900 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
|
1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Somnolence, Convulsions... Other AEs: Somnolence (severe) Sources: Convulsions (severe) Numbness (severe) Paresthesia (severe) Weakness (severe) Paralysis (severe) |
1200 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1200 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
DLT: Weakness, Ataxia... Dose limiting toxicities: Weakness (2 patients) Sources: Ataxia (2 patients) Confusion (2 patients) Coma (2 patients) |
1800 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1800 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1800 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
DLT: Weakness, Ataxia... Dose limiting toxicities: Weakness (3 patients) Sources: Ataxia (3 patients) Confusion (3 patients) Coma (3 patients) |
2250 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 2250 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 2250 mg/m2, 1 times / day Sources: |
unhealthy, child |
Other AEs: Somnolence... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Convulsions | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Numbness | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Paralysis | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Paresthesia | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Somnolence | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Weakness | severe | 1500 mg/m2 3 times / 3 weeks multiple, intravenous Recommended Dose: 1500 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1500 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Ataxia | 2 patients DLT |
1200 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1200 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Coma | 2 patients DLT |
1200 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1200 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Confusion | 2 patients DLT |
1200 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1200 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Weakness | 2 patients DLT |
1200 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1200 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1200 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Ataxia | 3 patients DLT |
1800 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1800 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1800 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Coma | 3 patients DLT |
1800 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1800 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1800 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Confusion | 3 patients DLT |
1800 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1800 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1800 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Weakness | 3 patients DLT |
1800 mg/m2 3 times / 3 weeks multiple, intravenous Dose: 1800 mg/m2, 3 times / 3 weeks Route: intravenous Route: multiple Dose: 1800 mg/m2, 3 times / 3 weeks Sources: |
unhealthy, adult |
Somnolence | severe, 1 patient | 2250 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 2250 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 2250 mg/m2, 1 times / day Sources: |
unhealthy, child |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 46.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0 |
no |
PubMed
Title | Date | PubMed |
---|---|---|
Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes. | 2001 Dec |
|
Nucleoside analogues in the treatment of haematological malignancies. | 2001 Jun |
|
CD4-CD8-"Double-negative" cutaneous T-cell lymphomas share common histologic features and an aggressive clinical course. | 2002 Feb |
|
Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. | 2002 Jun 1 |
|
Gateways to clinical trials. | 2003 Nov |
|
Purine nucleoside antimetabolites in development for the treatment of cancer. | 2004 Jun |
|
New nucleoside analogs in the treatment of hematological disorders. | 2004 May-Jun |
|
Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias. | 2005 Jun |
|
Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. | 2005 May 20 |
|
Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. | 2005 May 20 |
|
Purine nucleoside analogues for the treatment of hematological malignancies: pharmacology and clinical applications. | 2005 Sep |
|
Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukaemia and lymphoma. | 2006 Dec |
|
Nelarabine (Arranon) for T-cell acute lymphoblastic leukemia. | 2006 Feb 13 |
|
New drug to treat rare leukemia and lymphoma. | 2006 Jan-Feb |
|
Nelarabine use in leukemias. | 2006 Jul |
|
Gateways to clinical trials. | 2006 Jun |
|
Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents. | 2006 May |
|
Clofarabine and nelarabine: two new purine nucleoside analogs. | 2006 Nov |
|
The legacy of great science: the work of Nobel Laureate Gertrude Elion lives on. | 2006 Oct |
|
Milestones in oncology: introducing a new section. | 2006 Oct |
|
Nelarabine in the treatment of refractory T-cell malignant diseases. | 2006 Sep |
|
Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. | 2006 Sep 15 |
|
Clinical management of T-cell malignancies: current perspectives, key issues, and emerging therapies. | 2007 Dec |
|
Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine. | 2007 Dec |
|
Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901. | 2007 Jan |
|
Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. | 2007 Jun 15 |
|
Nelarabine. | 2008 |
|
Treating refractory leukemias in childhood, role of clofarabine. | 2008 Apr |
|
Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development. | 2008 Apr |
|
FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. | 2008 Jun |
|
Novel purine nucleoside analogues for hematological malignancies. | 2008 Jun |
|
Phase I trial of nelarabine in indolent leukemias. | 2008 Mar 1 |
|
Gateways to clinical trials. | 2008 May |
|
[Severe liver injury following nelarabine chemotherapy for T-cell lymphoblastic lymphoma]. | 2009 Jan |
|
Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature. | 2009 Jul |
|
Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. | 2009 Mar 23 |
|
New trends in nucleoside biotechnology. | 2010 Jul |
|
Use of clofarabine for acute childhood leukemia. | 2010 Jun 24 |
|
Application of new drugs in chronic lymphocytic leukemia. | 2010 May 10 |
|
Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia. | 2010 Oct 28 |
|
Rare tumors research in emerging countries. | 2010 Sep 30 |
|
Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature. | 2015 Aug |
Sample Use Guides
Adult: 1,500 mg/m² over 2 hours on Days 1, 3, and 5 repeated every 21 days
Pediatric: 650 mg/m² over 1 hour daily for 5 consecutive days repeated every 21 days
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/17391490
The in vitro efficacy of nelarabine was assessed in a panel of acute lymphoblastic leukaemia (ALL) cell lines. IC50 values were 0.067-2.15 uM.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:13:47 GMT 2025
by
admin
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Mon Mar 31 18:13:47 GMT 2025
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Record UNII |
60158CV180
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
125999
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WHO-ATC |
L01BB07
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EU-Orphan Drug |
EU/3/05/293
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NDF-RT |
N0000175595
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NCI_THESAURUS |
C1556
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EMA ASSESSMENT REPORTS |
ATTRIANCE (AUTHORIZED: PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA)
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LIVERTOX |
NBK548515
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WHO-VATC |
QL01BB07
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NDF-RT |
N0000000233
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FDA ORPHAN DRUG |
184404
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Code System | Code | Type | Description | ||
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C104457
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100000085469
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NELARABINE
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3011155
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DB01280
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60158CV180
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m7797
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7704
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60158CV180
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63612
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SUB09188MIG
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274771
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DTXSID6046842
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7090
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686673
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121032-29-9
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755985
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CHEMBL1201112
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1892
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C1704
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759876
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Related Record | Type | Details | ||
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BINDER->LIGAND |
Plasma protein binding is independent on nelarabine concentrations.
BINDING
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EXCRETED UNCHANGED |
URINE
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE ACTIVE -> PRODRUG |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE DOSE ADMINISTRATION |
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