Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C11H15N5O5 |
Molecular Weight | 297.2677 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COc1c2c([nH]c(=N)n1)n(cn2)[C@@]3([H])[C@]([H])([C@@]([H])([C@@]([H])(CO)O3)O)O
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 | 297.2677 |
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 Date1.1304576E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
52 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16953392 |
35 mg/kg single, intravenous dose: 35 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE blood | Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2820 μM × min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16953392 |
35 mg/kg single, intravenous dose: 35 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE blood | Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16953392 |
35 mg/kg single, intravenous dose: 35 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
NELARABINE blood | Macaca mulatta population: HEALTHY age: ADULT sex: 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 n = 2 Health Status: unhealthy Age Group: adult Population Size: 2 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 n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: |
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 n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: |
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 n = 1 Health Status: unhealthy Age Group: child Population Size: 1 Sources: |
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 n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: |
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 n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: |
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 n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: |
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 n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: |
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 n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: |
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 n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: |
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 n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: |
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 n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: |
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 n = 1 Health Status: unhealthy Age Group: child Population Size: 1 Sources: |
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 |
---|---|---|
Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells. | 2001 Apr 15 |
|
Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes. | 2001 Dec |
|
Purine nucleoside antimetabolites in development for the treatment of cancer. | 2004 Jun |
|
Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias. | 2005 Jun |
|
Nelarabine. | 2006 Jan |
|
New drug to treat rare leukemia and lymphoma. | 2006 Jan-Feb |
|
Nelarabine use in leukemias. | 2006 Jul |
|
Gateways to clinical trials. | 2006 Jun |
|
New drugs: abatacept, sorafenib, and nelarabine. | 2006 Mar-Apr |
|
Nelarabine: a new purine analog in the treatment of hematologic malignancies. | 2006 Sep |
|
Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. | 2007 Dec |
|
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 |
|
Plasma and cerebrospinal fluid pharmacokinetics of nelarabine in nonhuman primates. | 2007 May |
|
Nelarabine activity in acute biphenotypic leukemia. | 2007 Nov |
|
Cytotoxic nucleoside analogues: different strategies to improve their clinical efficacy. | 2008 |
|
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 |
|
Gateways to clinical trials. | 2008 Jan-Feb |
|
Phase I trial of nelarabine in indolent leukemias. | 2008 Mar 1 |
|
Gateways to clinical trials. | 2008 May |
|
Nelarabine: new drug. T-lymphoblastic leukaemia/lymphoma: more evaluation needed. | 2009 Feb |
|
Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. | 2009 Feb 18 |
|
[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 |
|
Glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia is associated with a proliferative metabolism. | 2009 Jun 16 |
|
Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. | 2009 Oct |
|
Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis? | 2010 |
|
Complete paraplegia after nelarabine treatment in a T-cell acute lymphoblastic leukemia adult patient. | 2010 Aug |
|
Nelarabine in the treatment of refractory T-cell malignancies. | 2010 Dec 1 |
|
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 |
|
Towards the development of a rapid, portable, surface enhanced Raman spectroscopy based cleaning verification system for the drug nelarabine. | 2010 Sep |
|
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
Fri Jun 25 21:58:40 UTC 2021
by
admin
on
Fri Jun 25 21:58:40 UTC 2021
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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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-
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Classification Tree | Code System | Code | ||
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WHO-ATC |
L01BB07
Created by
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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)
Created by
admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
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FDA ORPHAN DRUG |
125999
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LIVERTOX |
674
Created by
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WHO-VATC |
QL01BB07
Created by
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NDF-RT |
N0000000233
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FDA ORPHAN DRUG |
184404
Created by
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Code System | Code | Type | Description | ||
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C104457
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NELARABINE
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3011155
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DB01280
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PRIMARY | |||
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M7797
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PRIMARY | Merck Index | ||
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7704
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PRIMARY | |||
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60158CV180
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SUB09188MIG
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274771
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121032-29-9
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7090
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121032-29-9
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CHEMBL1201112
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1892
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PRIMARY | |||
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C1704
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PRIMARY |
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 |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
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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