nelarabine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
arabinofuranosyl derivatives 1892 121032-29-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nelarabine
  • arranon
  • nelzarabine
  • atriance
prodrug of ara-G
  • Molecular weight: 297.27
  • Formula: C11H15N5O5
  • CLOGP: -0.39
  • LIPINSKI: 0
  • HAC: 10
  • HDO: 4
  • TPSA: 148.77
  • ALOGS: -1.33
  • ROTB: 3
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 2.97 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 6.60 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 4.23 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 11 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.90 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 81 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.80 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.50 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.474 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 29.785 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 1.016 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.183 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 79.210 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 86.720 % High 1
herg hERG pIC50 3.793 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.288 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.327 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 69.660 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP2K6,MAP3K21,MAPK7,NTRK1,NTRK2,PDK1,PDK2,PIK3CD,PRKDC 21
kinase-selectivity-class MAP2K6,MAP3K21,PDK1 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.639 High 1
mh-clint Mouse hepatocyte intrinsic clearance 1.439 High 1
mppb Mouse plasma protein binding (% unbound) 89.270 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.203 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 86.800 % High 1
rh-clint Rat hepatocyte intrinsic clearance 2.023 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 93.450 % High 1
rppb Rat plasma protein binding (% unbound) 85.310 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 895.365 uM High 1

Approvals:

DateAgencyCompanyOrphan
Oct. 28, 2005 FDA NOVARTIS PHARMS CORP
Aug. 22, 2007 EMA Sandoz Pharmaceuticals d.d.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myelopathy 127.93 63.70 22 625 3422 90624378
Subacute combined cord degeneration 94.31 63.70 12 635 229 90627571
Peripheral sensory neuropathy 77.65 63.70 17 630 9233 90618567

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myelopathy 122.95 42.92 28 1876 2863 42616568
Guillain-Barre syndrome 79.76 42.92 24 1880 7239 42612192
Fibrinous bronchitis 72.31 42.92 11 1893 116 42619315
Scedosporium infection 60.38 42.92 14 1890 1544 42617887
Neurotoxicity 58.50 42.92 26 1878 23625 42595806
Neuropathy peripheral 56.27 42.92 42 1862 101811 42517620
Febrile neutropenia 56.01 42.92 54 1850 185649 42433782
Leukoencephalopathy 48.52 42.92 15 1889 4939 42614492
Stenotrophomonas infection 48.35 42.92 14 1890 3690 42615741
Peripheral sensory neuropathy 47.57 42.92 17 1887 8745 42610686
Ataxia 47.29 42.92 20 1884 16105 42603326

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myelopathy 243.53 43.67 49 2464 5527 110581259
Peripheral sensory neuropathy 137.76 43.67 38 2475 16642 110570144
Neurotoxicity 129.53 43.67 45 2468 42162 110544624
Guillain-Barre syndrome 129.37 43.67 33 2480 10711 110576075
Febrile neutropenia 101.85 43.67 72 2441 316695 110270091
Subacute combined cord degeneration 89.97 43.67 14 2499 354 110586432
Fibrinous bronchitis 77.47 43.67 11 2502 145 110586641
Neuropathy peripheral 77.35 43.67 49 2464 179228 110407558
Peripheral motor neuropathy 76.97 43.67 18 2495 4068 110582718
Scedosporium infection 63.43 43.67 14 2499 2444 110584342
Hypertriglyceridaemia 60.40 43.67 20 2493 16134 110570652
Muscular weakness 58.59 43.67 47 2466 248421 110338365
Polyneuropathy 57.26 43.67 23 2490 31989 110554797
Stenotrophomonas infection 51.35 43.67 14 2499 5844 110580942
Sensory loss 51.15 43.67 19 2494 21438 110565348
Pseudomonal bacteraemia 50.50 43.67 13 2500 4358 110582428
Ataxia 48.26 43.67 20 2493 30088 110556698

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01BB07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Purine analogues
FDA MoA N0000000233 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000175595 Nucleoside Metabolic Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:59517 DNA synthesis inhibitor

Related Drugs by ATC class:

L01BB Purine analogues 5 drugs
cladribineclofarabinefludarabine phosphatemercaptopurinethioguanine

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
T-cell acute lymphoblastic leukemia indication 277575008
Precursor T-cell lymphoblastic lymphoma indication 421246008
Hyperbilirubinemia contraindication 14783006 DOID:2741
Peripheral demyelinating neuropathy contraindication 23414001 DOID:5214
Demyelination contraindication 32693004
Dehydration contraindication 34095006
Mental handicap contraindication 47437004
Hepatic failure contraindication 59927004
Seizure disorder contraindication 128613002
Intrathecal injection of chemotherapeutic agent contraindication 171765004
Impaired renal function disorder contraindication 197663003
Anemia contraindication 271737000 DOID:2355
Drowsy contraindication 271782001
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Peripheral nerve disease contraindication 302226006
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Radiation Therapy of Cranium contraindication
Severe Leukopenia contraindication
Radiation Therapy of Vertebral Column contraindication
Chemotherapy-Induced Hyperuricemia contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.67 acidic
pKa2 12.33 acidic
pKa3 13.34 acidic
pKa4 3.39 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

None

External reference:

IDSource
4025093 VUID
N0000175345 NUI
D05134 KEGG_DRUG
4025093 VANDF
C0907349 UMLSCUI
CHEMBL1201112 ChEMBL_ID
DB01280 DRUGBANK_ID
C104457 MESH_SUPPLEMENTAL_RECORD_UI
3011155 PUBCHEM_CID
7090 IUPHAR_LIGAND_ID
7704 INN_ID
60158CV180 UNII
274771 RXNORM
20608 MMSL
354214 MMSL
72483 MMSL
d05655 MMSL
011068 NDDF
418538001 SNOMEDCT_US
418784008 SNOMEDCT_US
C0050203 UMLSCUI
CHEBI:63612 CHEBI
38819-10-2 SECONDARY_CAS_RN
135499520 PUBCHEM_CID
0Z99WX0GPF UNII

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Arranon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0683 INJECTION 5 mg INTRAVENOUS NDA 30 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 14789-114 INJECTION 5 mg INTRAVENOUS ANDA 28 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 25021-259 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 31 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 39822-0650 INJECTION 5 mg INTRAVENOUS ANDA 32 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 43598-142 INJECTION 5 mg INTRAVENOUS ANDA 28 sections
NELARABINE Human Prescription Drug Label 1 46708-813 INJECTION 5 mg INTRAVENOUS ANDA 27 sections
NELARABINE Human Prescription Drug Label 1 62332-813 INJECTION 5 mg INTRAVENOUS ANDA 26 sections
Arranon HUMAN PRESCRIPTION DRUG LABEL 1 66758-165 INJECTION 5 mg INTRAVENOUS NDA 30 sections
Nelarabine Human Prescription Drug Label 1 68083-233 INJECTION 5 mg INTRAVENOUS ANDA 27 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 70121-1743 INJECTION 5 mg INTRAVENOUS ANDA 28 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 70710-1726 INJECTION 5 mg INTRAVENOUS ANDA 26 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 70710-1839 INJECTION 5 mg INTRAVENOUS ANDA 26 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 70771-1685 INJECTION 5 mg INTRAVENOUS ANDA 1 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 71288-165 INJECTION 5 mg INTRAVENOUS ANDA 28 sections
Nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 71288-165 INJECTION 5 mg INTRAVENOUS ANDA 28 sections
NELARABINE Human Prescription Drug Label 1 72205-154 INJECTION 5 mg INTRAVENOUS ANDA 25 sections
nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 81927-111 INJECTION 5 mg INTRAVENOUS ANDA 29 sections
nelarabine HUMAN PRESCRIPTION DRUG LABEL 1 81927-375 INJECTION 5 mg INTRAVENOUS ANDA 29 sections