NAV

Nelarabine

Identification

Summary

Nelarabine is a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments.

Brand Names
Arranon, Atriance
Generic Name
Nelarabine
DrugBank Accession Number
DB01280
Background

Nelarabine is an antineoplastic agent that is typically used to treat acute T-cell lymphoblastic leukemia, particularly T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), in both adult and pediatric patients whose disease has not responded to or has relapsed following at least two chemotherapy regimens.14 T-cell acute lymphoblastic leukemia and lymphoma are relatively rare T-cells malignancy, with only 20 to 25% of patients diagnosed with acute lymphoblastic leukemia and 1.7% of patients diagnosed with non-Hodgkin's lymphoma having this T-cells variation of the disease.2 Due to the rarity of these T-cell malignancies, nelarabine was first granted orphan drug status and a fast-track designation by the FDA to address the unmet therapeutic needs of these cancers.1

Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in the inhibition of DNA synthesis and cytotoxicity.14 Nelarabine preferentially accumulates in T-cells since T-cells have a higher expression of enzymes that convert nelarabine to the active purine analog form, making them effective against T-cells malignancies.1,4 Results from 2 phase 2 studies on adult and pediatric T-ALL/T-LBL indicated that nelarabine can yield a 13% complete response (CR) rate in pediatric patients and 18% in adult patients, albeit with serious hematological and neurological adverse events.12

Nelarabine was first granted accelerated approval by the FDA on October 28, 2005, and was manufactured under the trademark name ARRANON by GlaxoSmithKline.11 Subsequently, nelarabine was also approved by both Health Canada and European Medicines Agency in 2007 under the trademark name ATRIANCE.17,18

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 297.2673
Monoisotopic: 297.107318615
Chemical Formula
C11H15N5O5
Synonyms
  • 2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine
  • Nelarabina
  • Nelarabine
  • Nelzarabine
External IDs
  • 506U
  • 506U78
  • GW-506U78
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Pharmacology

Indication

ARRANON is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.14

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofT-cell lymphoblastic lymphoma••••••••••••••••••••••• •••••• •••••••••••••••• ••••• •• ••••• ••••• •• •••••••• •••••••••••• •••••••• •• • •••••••• ••••••••••••••••••
Treatment ofT-cell acute lymphoblastic leukemia (t-all)••••••••••••••••••••••• •••••• •••••••••••••••• ••••• •• ••••• ••••• •• •••••••• •••••••••••• •••••••• •• • •••••••• ••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.14 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).14 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.14 Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts.1,4

Mechanism of action

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. As a nucleoside analog, Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA.3,4,5,6 Due to its intact 3'-OH group, ara-GTP can be incorporated into the growing DNA strand without absolute chain termination.7 Despite that, the inclusion of ara-GTP into DNA strand can impair proper DNA repair processes, although the exact mechanism is not well understood, leading to inhibition of DNA elongation, apoptosis, and cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.2,3,4,7

TargetActionsOrganism
ADNA
incorporation into and destabilization
Humans
ADNA polymerase alpha catalytic subunit
inhibitor
Humans
ADNA ligase 1
inhibitor
Humans
ADNA primase small subunit
inhibitor
Humans
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Humans
Absorption

Following intravenous administration of nelarabine to adult patients with refractory leukemia or lymphoma, plasma ara-G Cmax values generally occurred at the end of the nelarabine infusion and were generally higher than nelarabine Cmax values, suggesting rapid and extensive conversion of nelarabine to ara-G. Mean plasma nelarabine and ara-G Cmax values were 5.0 ± 3.0 mcg/mL and 31.4 ± 5.6 mcg/mL, respectively, after a 1,500 mg/m2 nelarabine dose infused over 2 hours in adult patients.14 The area under the concentration-time curve (AUC) of ara-G is 37 times higher than that for nelarabine on Day 1 after nelarabine IV infusion of 1,500 mg/m2 dose (162 ± 49 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL, respectively). Comparable Cmax and AUC values were obtained for nelarabine between Days 1 and 5 at the nelarabine adult dosage of 1,500 mg/m2, indicating that nelarabine does not accumulate after multiple dosing. There are not enough ara-G data to make a comparison between Day 1 and Day 5.14 After a nelarabine adult dose of 1,500 mg/m2, intracellular Cmax for ara-GTP appeared within 3 to 25 hours on Day 1. Exposure (AUC) to intracellular ara-GTP was 532 times higher than that for nelarabine and 14 times higher than that for ara-G (2,339 ± 2,628 mcg.h/mL versus 4.4 ± 2.2 mcg.h/mL and 162 ± 49 mcg.h/mL, respectively).14

Volume of distribution

Nelarabine and ara-G are extensively distributed throughout the body. For nelarabine, Vss values were 197 ± 216 L/m2 in adult patients. For ara-G, Vss/F values were 50 ± 24 L/m2 in adult patients.14

Protein binding

Nelarabine and ara-G are not substantially bound to human plasma proteins (< 25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 µM.14

Metabolism

The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolyzed to form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid.14 Ring opening of uric acid followed by further oxidation results in the formation of allantoin.16

Ring opening of uric acid followed by further oxidation results in the formation of allantoin.

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Route of elimination

Nelarabine and ara-G are partially eliminated by the kidneys.14 Mean urinary excretion of nelarabine and ara-G was 6.6 ± 4.7% and 27 ± 15% of the administered dose, respectively, in 28 adult patients over the 24 hours after nelarabine infusion on Day 1.14

Half-life

Nelarabine and ara-G are rapidly eliminated from plasma with a mean half-life of 18 minutes and 3.2 hours, respectively, in adult patients.14 For pediatric patients, the half-life of nelarabine and ara-G are 13 minutes and 2 hours, respectively.14 Because the intracellular levels of ara-GTP were so prolonged, its elimination half-life could not be accurately estimated.14

Clearance

Renal clearance averaged 24 ± 23 L/h for nelarabine and 6.2 ± 5.0 L/h for ara-G in 21 adult patients. Combined Phase I pharmacokinetic data at nelarabine doses of 199 to 2,900 mg/m2 (n = 66 adult patients) indicate that the mean clearance (CL) of nelarabine is 197 ± 189 L/h/m2 on Day 1. The apparent clearance of ara-G (CL/F) is 10.5 ± 4.5 L/h/m2 on Day 1.14 For pediatric patients receiving at a dose of 104 to 2,900 mg/m2, the combined Phase I pharmacokinetic data indicate that the mean clearance (CL) of nelarabine is 259 ± 409 L/h/m2, 30% higher than in adult patients. The apparent clearance of ara-G on day 1 is also higher in pediatric patients than in adult patients, estimated to be 11.3 ± 4.2 L/h/m2.14

Adverse Effects
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Toxicity

A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbataceptThe risk or severity of adverse effects can be increased when Nelarabine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Nelarabine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Nelarabine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Nelarabine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Nelarabine.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArranonInjection5 mg/1mLIntravenousGlaxosmithkline Inc2006-01-192018-12-31US flag
ArranonInjection5 mg/1mLIntravenousNovartis Pharmaceuticals Corporation2016-10-05Not applicableUS flag
AtrianceInjection, solution5 mg/mlIntravenousSandoz Pharmaceuticals D.D.2016-09-20Not applicableEU flag
AtrianceSolution5 mg / mLIntravenousSandoz Canada Incorporated2008-01-17Not applicableCanada flag
AtrianceInjection, solution5 mg/mlIntravenousSandoz Pharmaceuticals D.D.2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NelarabineInjection5 mg/1mLIntravenousDr. Reddy's Laboratories, Inc.2023-01-09Not applicableUS flag
NelarabineInjection5 mg/1mLIntravenousZydus Lifesciences Limited2021-11-17Not applicableUS flag
NelarabineInjection5 mg/1mLIntravenousNexus Pharmaceuticals LLC2023-12-26Not applicableUS flag
NelarabineInjection5 mg/1mLIntravenousShorla Oncology Inc.2023-03-15Not applicableUS flag
NelarabineInjection5 mg/1mLIntravenousZydus Pharmaceuticals USA Inc.2022-06-24Not applicableUS flag

Categories

ATC Codes
L01BB07 — Nelarabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleosides
Sub Class
Not Available
Direct Parent
Purine nucleosides
Alternative Parents
Glycosylamines / Pentoses / Hypoxanthines / Aminopyrimidines and derivatives / Alkyl aryl ethers / N-substituted imidazoles / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds
show 5 more
Substituents
Alcohol / Alkyl aryl ether / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Ether / Glycosyl compound / Heteroaromatic compound
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
purine nucleoside, monosaccharide derivative, beta-D-arabinoside (CHEBI:63612)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
60158CV180
CAS number
121032-29-9
InChI Key
IXOXBSCIXZEQEQ-UHTZMRCNSA-N
InChI
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
IUPAC Name
(2R,3S,4S,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
SMILES
COC1=NC(N)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O

References

General References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. doi: 10.1016/j.hoc.2009.07.008. [Article]
  3. Roecker AM, Allison JC, Kisor DF: Nelarabine: efficacy in the treatment of clinical malignancies. Future Oncol. 2006 Aug;2(4):441-8. [Article]
  4. Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. [Article]
  5. Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Article]
  6. Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Article]
  7. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]
  8. Sigalas P, Tourvas AD, Moulakakis A, Pangalis G, Kontopidou F: Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature. Leuk Res. 2009 Jul;33(7):e61-3. doi: 10.1016/j.leukres.2008.12.005. Epub 2009 Jan 21. [Article]
  9. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [Article]
  10. Chang JE, Medlin SC, Kahl BS, Longo WL, Williams EC, Lionberger J, Kim K, Kim J, Esterberg E, Juckett MB: Augmented and standard Berlin-Frankfurt-Munster chemotherapy for treatment of adult acute lymphoblastic leukemia. Leuk Lymphoma. 2008 Dec;49(12):2298-307. doi: 10.1080/10428190802517732. [Article]
  11. Cohen MH, Johnson JR, Justice R, Pazdur R: FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. Oncologist. 2008 Jun;13(6):709-14. doi: 10.1634/theoncologist.2006-0017. [Article]
  12. Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G: Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. doi: 10.1111/bjh.14874. Epub 2017 Aug 2. [Article]
  13. FDA Approved Drug Products: NELARABINE- nelarabine injection [Link]
  14. FDA Approved Drug Products: ARRANON (nelarabine) injection, for intravenous use 2 [Link]
  15. Health Canada Approved Drug Proucts: ATRIANCE (Nelarabine) injection, for intravenous use [Link]
  16. FDA Approved Drug Products: ARRANON® (nelarabine) Injection FOR INTRAVENOUS USE [Link]
  17. Fact sheet - Atriance (nelarabine) [Link]
  18. Atriance [Link]
Human Metabolome Database
HMDB0015401
KEGG Drug
D05134
PubChem Compound
3011155
PubChem Substance
46506325
ChemSpider
2280207
BindingDB
50247985
RxNav
274771
ChEBI
63612
ChEMBL
CHEMBL1201112
ZINC
ZINC000003823492
Therapeutic Targets Database
DAP000985
PharmGKB
PA164752425
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nelarabine
FDA label
Download (282 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoblastic Lymphoma1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3Active Not RecruitingTreatmentLeukemias / Mucositis / Oral Complications1
3Active Not RecruitingTreatmentT-cell Acute Lymphoblastic Leukemia / T-cell Lymphoblastic Lymphoma1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Angioimmunoblastic T-cell Lymphoma (AITL) / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides and Sezary Syndrome / Small Intestine Lymphoma / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage I Mycosis Fungoides/Sezary Syndrome / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage II Mycosis Fungoides/Sezary Syndrome / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage III Mycosis Fungoides/Sezary Syndrome / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • GlaxoSmithKline Inc.
Dosage Forms
FormRouteStrength
InjectionIntravenous5 mg/1mL
Injection, solutionIntravenous5 mg/ml
Injection, solutionIntravenous; Parenteral5 MG/ML
SolutionIntravenous5 mg / mL
InjectionIntravenous250 mg/50mL
Injection, solutionIntravenous250 mg/50ml
Prices
Unit descriptionCostUnit
Arranon 250 mg vial12.75USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5492897No1996-02-202013-02-20US flag
US5424295No1995-06-132017-06-13US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)209-217 °C (with decomposition)L40878
water solubilitySlightly soluble to soluble in waterL40878
Predicted Properties
PropertyValueSource
Water Solubility13.9 mg/mLALOGPS
logP-0.81ALOGPS
logP-1.6Chemaxon
logS-1.3ALOGPS
pKa (Strongest Acidic)12.45Chemaxon
pKa (Strongest Basic)4.47Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area148.77 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity69.6 m3·mol-1Chemaxon
Polarizability28.34 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9776
Blood Brain Barrier+0.8171
Caco-2 permeable-0.8263
P-glycoprotein substrateNon-substrate0.5664
P-glycoprotein inhibitor INon-inhibitor0.9525
P-glycoprotein inhibitor IINon-inhibitor0.9667
Renal organic cation transporterNon-inhibitor0.929
CYP450 2C9 substrateNon-substrate0.8604
CYP450 2D6 substrateNon-substrate0.8369
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8729
CYP450 2C9 inhibitorNon-inhibitor0.9149
CYP450 2D6 inhibitorNon-inhibitor0.937
CYP450 2C19 inhibitorNon-inhibitor0.9352
CYP450 3A4 inhibitorNon-inhibitor0.9568
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9794
Ames testNon AMES toxic0.8799
CarcinogenicityNon-carcinogens0.9252
BiodegradationNot ready biodegradable0.9723
Rat acute toxicity1.9319 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9497
hERG inhibition (predictor II)Non-inhibitor0.8711
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0ab9-9160000000-faf81feea076fd7f2c2e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-1910000000-d09b09e2c32a65f2ac55
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0950000000-2ab047053d019dcee056
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001j-0960000000-ce81b1beb23d7d7e9782
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-e0eaf9830fadb403b0a4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-2900000000-62f968666993161ea368
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-06si-1910000000-8e57c8d0c05590657b26
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-08fr-0900000000-390c3450c741eb3e5d74
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-178.6035089
predicted
DarkChem Lite v0.1.0
[M-H]-176.5537089
predicted
DarkChem Lite v0.1.0
[M-H]-159.89207
predicted
DeepCCS 1.0 (2019)
[M+H]+178.5386089
predicted
DarkChem Lite v0.1.0
[M+H]+175.9248089
predicted
DarkChem Lite v0.1.0
[M+H]+162.28764
predicted
DeepCCS 1.0 (2019)
[M+Na]+179.0392089
predicted
DarkChem Lite v0.1.0
[M+Na]+176.6887089
predicted
DarkChem Lite v0.1.0
[M+Na]+169.192
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Incorporation into and destabilization
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  4. DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. doi: 10.1016/j.hoc.2009.07.008. [Article]
  5. Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. [Article]
  6. Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Article]
  7. Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Article]
  8. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]
  9. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [Article]
Details2. DNA polymerase alpha catalytic subunit
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein kinase binding
Specific Function
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subuni...
Gene Name
POLA1
Uniprot ID
P09884
Uniprot Name
DNA polymerase alpha catalytic subunit
Molecular Weight
165911.405 Da
References
  1. Ono K, Ohashi A, Yamamoto A, Matsukage A, Takahasi T, Saneyoshi M, Ueda T: Inhibitory effects of 9-beta-D-arabinofuranosylguanine 5'-triphosphate and 9-beta-D-arabinofuranosyladenine 5'-triphosphate on DNA polymerases from murine cells and oncornavirus. Cancer Res. 1979 Nov;39(11):4673-80. [Article]
  2. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  3. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]
  4. Rodriguez CO Jr, Stellrecht CM, Gandhi V: Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood. 2003 Sep 1;102(5):1842-8. Epub 2003 May 15. [Article]
Details3. DNA ligase 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair.
Gene Name
LIG1
Uniprot ID
P18858
Uniprot Name
DNA ligase 1
Molecular Weight
101735.11 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]
Details4. DNA primase small subunit
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex - primosome/replisome) which play an essential role in the initiation of DNA synthesis (PubMed:9268648, PubMed:9705292, PubMed:17893144, PubMed:24043831, PubMed:26975377, PubMed:25550159, PubMed:31479243, PubMed:33060134). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144). Synthesizes 9-mer RNA primers (also known as the 'unit length' RNA primers). Incorporates only ribonucleotides in the presence of ribo- and deoxy-nucleotide triphosphates (rNTPs, dNTPs) (PubMed:26975377). Requires template thymine or cytidine to start the RNA primer synthesis, with an adenine or guanine at its 5'-end (PubMed:25550159, PubMed:26975377). Binds single stranded DNA (By similarity).
Specific Function
Dna primase activity
Gene Name
PRIM1
Uniprot ID
P49642
Uniprot Name
DNA primase small subunit
Molecular Weight
49901.635 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]
Details5. Ribonucleoside-diphosphate reductase large subunit
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name
RRM1
Uniprot ID
P23921
Uniprot Name
Ribonucleoside-diphosphate reductase large subunit
Molecular Weight
90069.375 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. Curbo S, Karlsson A: Nelarabine: a new purine analog in the treatment of hematologic malignancies. Rev Recent Clin Trials. 2006 Sep;1(3):185-92. [Article]

Enzymes

Details1. Adenosine deaminase
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, an...
Gene Name
ADA
Uniprot ID
P00813
Uniprot Name
Adenosine deaminase
Molecular Weight
40764.13 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. doi: 10.1016/j.hoc.2009.07.008. [Article]
  3. Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Article]
  4. Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Article]
  5. Cohen MH, Johnson JR, Justice R, Pazdur R: FDA drug approval summary: nelarabine (Arranon) for the treatment of T-cell lymphoblastic leukemia/lymphoma. Oncologist. 2008 Jun;13(6):709-14. doi: 10.1634/theoncologist.2006-0017. [Article]
  6. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [Article]
Details2. Deoxycytidine kinase
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. doi: 10.1016/j.hoc.2009.07.008. [Article]
  3. Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Article]
  4. Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Article]
  5. DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA: 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. Blood. 2007 Jun 15;109(12):5136-42. Epub 2007 Mar 7. [Article]
Details3. Deoxyguanosine kinase, mitochondrial
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nucleoside kinase activity
Specific Function
Required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name
DGUOK
Uniprot ID
Q16854
Uniprot Name
Deoxyguanosine kinase, mitochondrial
Molecular Weight
32055.53 Da
References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [Article]
  2. DeAngelo DJ: Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am. 2009 Oct;23(5):1121-35, vii-viii. doi: 10.1016/j.hoc.2009.07.008. [Article]
  3. Reilly KM, Kisor DF: Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28. [Article]
  4. Cooper TM: Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Ther Clin Risk Manag. 2007 Dec;3(6):1135-41. [Article]
  5. DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA: 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. Blood. 2007 Jun 15;109(12):5136-42. Epub 2007 Mar 7. [Article]

Carriers

Details1. Equilibrative nucleoside transporter 1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Yamauchi T, Uzui K, Nishi R, Shigemi H, Ueda T: Reduced drug incorporation into DNA and antiapoptosis as the crucial mechanisms of resistance in a novel nelarabine-resistant cell line. BMC Cancer. 2014 Jul 29;14:547. doi: 10.1186/1471-2407-14-547. [Article]

Drug created at May 16, 2007 22:44 / Updated at April 15, 2023 22:28