U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of NELARABINE

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

HIDE SMILES / InChI

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

Curator's Comment:: Nelarabine is widely distributed throughout the body and lower levels detected in the CNS

Originator

Curator's Comment:: Nelarabine was transfered from GlaxoSmithKline to Novartis http://www.pharmaceutical-journal.com/news-and-analysis/notice-board/transfer-of-products-from-glaxosmithkline-to-novartis/20068469.article

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ARRANON

Approved Use

ARRANON 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 Date

1.1304576E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
52 μM
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

AUC

ValueDoseCo-administeredAnalytePopulation
2820 μM × min
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

T1/2

ValueDoseCo-administeredAnalytePopulation
25 min
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
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

Doses

DosePopulationAdverse 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)
Convulsions (severe)
Numbness (severe)
Paresthesia (severe)
Weakness (severe)
Paralysis (severe)
Sources:
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)
Ataxia (2 patients)
Confusion (2 patients)
Coma (2 patients)
Sources:
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)
Ataxia (3 patients)
Confusion (3 patients)
Coma (3 patients)
Sources:
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...
Other AEs:
Somnolence (severe, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
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
Patents

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
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 Fri Jun 25 21:58:40 UTC 2021
Edited
by admin
on Fri Jun 25 21:58:40 UTC 2021
Record UNII
60158CV180
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NELARABINE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
506U78
Code English
ARRANON
Brand Name English
NELARABINE [ORANGE BOOK]
Common Name English
NELARABINE [EMA EPAR]
Common Name English
NELARABINE [WHO-DD]
Common Name English
506U
Code English
ATTRIANCE
Brand Name English
NELARABINE [INN]
Common Name English
NELZARABINE
Common Name English
NELARABINE [MART.]
Common Name English
MAY
Code English
9H-PURIN-2-AMINE, 9-.BETA.-D-ARABINOFURANOSYL-6-METHOXY-
Systematic Name English
NELARABINE [MI]
Common Name English
NELARABINE [VANDF]
Common Name English
9-.BETA.-D-ARABINOFURANOSYL-6-METHOXY-9H-PURIN-2-AMINE
Common Name English
NSC-755985
Code English
NSC-686673
Code English
NSC-759876
Code English
NELARABINE [JAN]
Common Name English
NELARABINE [USAN]
Common Name English
GW-506U78
Code English
2-AMINO-9-.BETA.-D-ARABINOFURANOSYL-6-METHOXY-9H-PURINE
Systematic Name English
Classification Tree Code System Code
WHO-ATC L01BB07
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
EU-Orphan Drug EU/3/05/293
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
NDF-RT N0000175595
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
NCI_THESAURUS C1556
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
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
FDA ORPHAN DRUG 125999
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
LIVERTOX 674
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
WHO-VATC QL01BB07
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
NDF-RT N0000000233
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
FDA ORPHAN DRUG 184404
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
Code System Code Type Description
MESH
C104457
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
WIKIPEDIA
NELARABINE
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
PUBCHEM
3011155
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
DRUG BANK
DB01280
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
MERCK INDEX
M7797
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY Merck Index
INN
7704
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
FDA UNII
60158CV180
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
EVMPD
SUB09188MIG
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
RXCUI
274771
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY RxNorm
EPA CompTox
121032-29-9
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
IUPHAR
7090
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
CAS
121032-29-9
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201112
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
DRUG CENTRAL
1892
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
NCI_THESAURUS
C1704
Created by admin on Fri Jun 25 21:58:40 UTC 2021 , Edited by admin on Fri Jun 25 21:58:40 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
Plasma protein binding is independent on nelarabine concentrations.
BINDING
EXCRETED UNCHANGED
URINE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE ADMINISTRATION