NELARABINE

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 Search

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021877s005lbl.pdf

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 232 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18318562	Binding Agent 996

Conditions

Condition	Modality	Targets	Highest Phase	Product
T-cell acute lymphoblastic leukemia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021877s005lbl.pdf	Primary		Approved 8043	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

C_max

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

T_1/2

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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf	unhealthy, adult n = 2 Health Status: unhealthy Age Group: adult Population Size: 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf	Other AEs: Somnolence, Convulsions... Other AEs: Somnolence (severe) Convulsions (severe) Numbness (severe) Paresthesia (severe) Weakness (severe) Paralysis (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021877lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/15908649	unhealthy, adult n = 31 Health Status: unhealthy Age Group: adult Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/15908649	DLT: Weakness, Ataxia... Dose limiting toxicities: Weakness (2 patients) Ataxia (2 patients) Confusion (2 patients) Coma (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/15908649
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: https://pubmed.ncbi.nlm.nih.gov/15908649	unhealthy, adult n = 4 Health Status: unhealthy Age Group: adult Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/15908649	DLT: Weakness, Ataxia... Dose limiting toxicities: Weakness (3 patients) Ataxia (3 patients) Confusion (3 patients) Coma (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/15908649
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: https://pubmed.ncbi.nlm.nih.gov/15908649	unhealthy, child n = 1 Health Status: unhealthy Age Group: child Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15908649	Other AEs: Somnolence... Other AEs: Somnolence (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15908649

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1604	inhibitor 1702

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2A6 627 CYP2B6 717 CYP2C8 818 CYP2C19 1325 P-gp 1330 CYP 98	CYP 236 P-gp 1400

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2B6 884	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no [IC50 >100 uM]
CYP 132	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_Pharmr.pdf Page: 8.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 8, 48	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 236	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 46.0	no
P-gp 1400	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021877_s000_Arranon_BioPharmr.pdf Page: 47.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63612	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63612
ChemicalBook	CB01011878	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01011878
MolPort	MolPort-006-167-760	https://www.molport.com/shop/molecule-link/MolPort-006-167-760
Selleck Chemicals	Arranon	http://www.selleckchem.com/products/Arranon.html
ZINC	ZINC000003823492	http://zinc15.docking.org/substances/ZINC000003823492
eMolecules	32176516	https://www.emolecules.com/cgi-bin/more?vid=32176516

PubMed

Title	Date	PubMed
6-Methoxypurine arabinoside as a selective and potent inhibitor of varicella-zoster virus.	1991 May	1649571
Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias.	2005 Jun	15870141
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	15908649
Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity.	2006	17168705
Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukaemia and lymphoma.	2006 Dec	17107284
Nelarabine.	2006 Jan	16485343
New drug to treat rare leukemia and lymphoma.	2006 Jan-Feb	16532541
Nelarabine use in leukemias.	2006 Jul	16894400
Multifocal necrotizing leukoencephalopathy: An unusual complication of acute leukemia.	2006 Jul	16831976
Gateways to clinical trials.	2006 Jun	16845450
New drugs: abatacept, sorafenib, and nelarabine.	2006 Mar-Apr	16602235
Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents.	2006 May	16719832
Nelarabine: a new purine analog in the treatment of hematologic malignancies.	2006 Sep	18473971
Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma.	2006 Sep 15	17000665
Treatment of acute lymphoblastic leukaemia : a new era.	2007	17927282
In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia.	2007 Apr	17391490
Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.	2007 Dec	18516261
Clinical management of T-cell malignancies: current perspectives, key issues, and emerging therapies.	2007 Dec	18086345
Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine.	2007 Dec	18086342
Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901.	2007 Jan	17325852
The long and winding road of the clinical development of Nelarabine.	2007 Jan	17325839
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	17344466
Cytotoxic nucleoside analogues: different strategies to improve their clinical efficacy.	2008	18473803
Nelarabine.	2008	18318562
Treating refractory leukemias in childhood, role of clofarabine.	2008 Apr	18728851
Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development.	2008 Apr	18433608
Gateways to clinical trials.	2008 Jan-Feb	18389098
FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma.	2008 Jun	18586926
Novel purine nucleoside analogues for hematological malignancies.	2008 Jun	18537755
Phase I trial of nelarabine in indolent leukemias.	2008 Mar 1	18309944
Gateways to clinical trials.	2008 May	18773127
T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993).	2009 Dec 10	19828704
Development of fludarabine formulations in the treatment of chronic lymphocytic leukemia.	2009 Dec 29	20054443
Nelarabine: new drug. T-lymphoblastic leukaemia/lymphoma: more evaluation needed.	2009 Feb	19382393
Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia.	2009 Feb 18	20616909
[Severe liver injury following nelarabine chemotherapy for T-cell lymphoblastic lymphoma].	2009 Jan	19225230
Novel therapies for relapsed acute lymphoblastic leukemia.	2009 Jul	20425428
Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature.	2009 Jul	19157550
Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases.	2009 Mar 23	19325518
Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?	2010	20936157
Complete paraplegia after nelarabine treatment in a T-cell acute lymphoblastic leukemia adult patient.	2010 Aug	20658590
Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.	2010 Aug	20528871
A new high-performance liquid chromatography method determines low production of 9-beta-D-arabinofuranosylguanine triphosphate, an active metabolite of nelarabine, in adult T-cell leukemia cells.	2010 Feb	20043113
New trends in nucleoside biotechnology.	2010 Jul	22649640
Use of clofarabine for acute childhood leukemia.	2010 Jun 24	20631817
Application of new drugs in chronic lymphocytic leukemia.	2010 May 10	21415964
Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia.	2010 Oct 28	20979663
Towards the development of a rapid, portable, surface enhanced Raman spectroscopy based cleaning verification system for the drug nelarabine.	2010 Sep	20796200
Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature.	2015 Aug	24664478

Patents

Sample Use Guides

In Vivo Use Guide

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.

Name

Type

Language

NELARABINE

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