Identification
NameNelarabine
Accession NumberDB01280
TypeSmall Molecule
GroupsApproved, Investigational
Description

Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.

Structure
Thumb
Synonyms
2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine
Arranon
Nelzarabine
External IDs 506U / 506U78 / GW-506U78
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArranonInjection5 mg/mLIntravenousGlaxosmithkline Inc2006-01-192018-12-31Us
ArranonInjection5 mg/mLIntravenousNovartis2016-10-05Not applicableUs
AtrianceInjection, solution5 mg/mlIntravenousNovartis Europharm Limited2007-08-22Not applicableEu
AtrianceSolution5 mgIntravenousNovartis2008-01-17Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII60158CV180
CAS number121032-29-9
WeightAverage: 297.2673
Monoisotopic: 297.107318615
Chemical FormulaC11H15N5O5
InChI KeyIXOXBSCIXZEQEQ-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[[email protected]](CO)[C@@H](O)[C@@H]1O
Pharmacology
Indication

For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

Structured Indications
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. 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). 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 suggest that T-cells are particularly sensitive to nelarabine.

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. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNANucleotideyes
incorporation into and destabilization
Humannot applicabledetails
DNA polymerase alpha catalytic subunitProteinunknown
inhibitor
HumanP09884 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
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 mM.

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

SubstrateEnzymesProduct
Nelarabine
arabinofuranosylguanineDetails
Nelarabine
ara-G diphosphateDetails
Route of elimination

Excretion: Nelarabine and ara-G are partially eliminated by the kidneys.

Half life

Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.

Clearance
  • 197  +/-  189 L/h/m2 [Adult patients with refractory leukemia or lymphoma receiving doses of 199 to 2,900 mg/m2]
  • 259  +/-  409 L/h/m2 [Pediatric patients with refractory leukemia or lymphoma receiving doses of 104 to 2,900 mg/m2]
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.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Nelarabine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Nelarabine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Nelarabine.Approved
ClozapineThe risk or severity of adverse effects can be increased when Nelarabine is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Nelarabine.Approved, Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Nelarabine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Nelarabine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Nelarabine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Nelarabine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Nelarabine.Approved, Investigational
FingolimodNelarabine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Nelarabine is combined with G17DT.Investigational
INGN 201The risk or severity of adverse effects can be increased when Nelarabine is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Nelarabine is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Nelarabine is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Nelarabine.Withdrawn
NatalizumabThe risk or severity of adverse effects can be increased when Nelarabine is combined with Natalizumab.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Nelarabine.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Nelarabine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Nelarabine.Approved, Vet Approved
PentostatinPentostatin may decrease the antineoplastic activities of Nelarabine.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Nelarabine.Approved, Investigational
RindopepimutThe risk or severity of adverse effects can be increased when Nelarabine is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Nelarabine.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Nelarabine.Approved
SRP 299The risk or severity of adverse effects can be increased when Nelarabine is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Nelarabine.Approved, Investigational
TofacitinibNelarabine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Nelarabine.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [PubMed:18035189 ]
  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. [PubMed:19825456 ]
  3. Roecker AM, Allison JC, Kisor DF: Nelarabine: efficacy in the treatment of clinical malignancies. Future Oncol. 2006 Aug;2(4):441-8. [PubMed:16922610 ]
  4. Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. [PubMed:18318562 ]
  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. [PubMed:20616909 ]
  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. [PubMed:18516261 ]
  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. [PubMed:18473971 ]
  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. [PubMed:19157550 ]
  9. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [PubMed:16485343 ]
External Links
ATC CodesL01BB07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (282 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLeukemias1
1TerminatedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes1
1, 2TerminatedTreatmentRelapsed T-Cell Acute Lymphoblastic Leukemia / Relapsed T-Cell Lymphoblastic Lymphoma1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/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
2CompletedTreatmentLeukemias2
2CompletedTreatmentLeukemias / Malignant Lymphomas1
2CompletedTreatmentRecurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Lymphoblastic Lymphoma / T-cell Childhood Acute Lymphoblastic Leukemia1
2CompletedTreatmentT-ALL, T-NHL (Lymphoblastic)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, B-Cell / Leukemia, T-Cell / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAdult T Lymphoblastic Lymphoma / T-Acute Lymphoblastic Leukemia1
2RecruitingTreatmentLeukemia, Lymphoblastic, Acute / Leukemias / Lymphoma, Lymphoblastic1
2RecruitingTreatmentT-cell Adult Acute Lymphoblastic Leukemia1
2TerminatedTreatmentAngioimmunoblastic T-Cell Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
2TerminatedTreatmentRecurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome1
3Active Not RecruitingTreatmentAdult T Acute Lymphoblastic Leukemia / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Not Yet RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
3Unknown StatusTreatmentLeukemias / Mucositis / Oral Complications1
Not AvailableCompletedNot AvailableLeukemia, Lymphoblastic, Acute1
Not AvailableCompletedTreatmentLeukemias / Malignant Lymphomas1
Not AvailableCompletedTreatmentT-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableRecruitingNot AvailableCancers1
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
InjectionIntravenous5 mg/mL
Injection, solutionIntravenous5 mg/ml
SolutionIntravenous5 mg
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)
US5424295 No1997-06-132017-06-13Us
US5492897 No1993-02-202013-02-20Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)209-217 °C (with decomposition)Not Available
water solubilitySlightly soluble to soluble in waterNot Available
logP-1Not Available
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)3.47ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area148.77 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity69.6 m3·mol-1ChemAxon
Polarizability27.68 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-1910000000-d09b09e2c32a65f2ac55View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassNucleosides, nucleotides, and analogues
Sub ClassPurine nucleosides
Direct ParentPurine nucleosides
Alternative ParentsGlycosylamines / Pentoses / Hypoxanthines / Aminopyrimidines and derivatives / Alkyl aryl ethers / Primary aromatic amines / N-substituted imidazoles / Oxolanes / Heteroaromatic compounds / Secondary alcohols
SubstituentsPurine nucleoside / Glycosyl compound / N-glycosyl compound / Hypoxanthine / Pentose monosaccharide / Imidazopyrimidine / Purine / Alkyl aryl ether / Aminopyrimidine / Monosaccharide
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorspurine nucleoside, monosaccharide derivative, beta-D-arabinoside (CHEBI:63612 )

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [PubMed:17139284 ]
  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. [PubMed:17016423 ]
  3. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [PubMed:18035189 ]
  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. [PubMed:19825456 ]
  5. Sanford M, Lyseng-Williamson KA: Nelarabine. Drugs. 2008;68(4):439-47. [PubMed:18318562 ]
  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. [PubMed:20616909 ]
  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. [PubMed:18516261 ]
  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. [PubMed:18473971 ]
  9. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [PubMed:16485343 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha com...
Gene Name:
POLA1
Uniprot ID:
P09884
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. [PubMed:91427 ]
  2. Buie LW, Epstein SS, Lindley CM: Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Ther. 2007 Sep;29(9):1887-99. [PubMed:18035189 ]
  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. [PubMed:18473971 ]
  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. [PubMed:12750168 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
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, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.
Gene Name:
ADA
Uniprot ID:
P00813
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. [PubMed:18035189 ]
  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. [PubMed:19825456 ]
  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. [PubMed:20616909 ]
  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. [PubMed:18516261 ]
  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. [PubMed:18586926 ]
  6. Gandhi V, Keating MJ, Bate G, Kirkpatrick P: Nelarabine. Nat Rev Drug Discov. 2006 Jan;5(1):17-8. [PubMed:16485343 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
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. [PubMed:18035189 ]
  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. [PubMed:19825456 ]
  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. [PubMed:20616909 ]
  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. [PubMed:18516261 ]
  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. [PubMed:17344466 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
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. [PubMed:18035189 ]
  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. [PubMed:19825456 ]
  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. [PubMed:20616909 ]
  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. [PubMed:18516261 ]
  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. [PubMed:17344466 ]
Drug created on May 16, 2007 16:44 / Updated on June 24, 2017 13:16