Details of the Drug

General Information of Drug (ID: DMB6VEG)

• Drug Name: Nelarabine
• Synonyms: Arranon; ArranonG; Atriance; Nelzarabine; Nelarabine [USAN]; Nelzarabine [USAN]; GW 506U78; GW506U78; U78; Arranon (GlaxoSmithKline); Arranon (TN); Arranon, Nelarabine; Atriance (TN); GW-506U; GW-506U78; Nelarabine (INN); Nelzarabine (USAN); O-Methoxydeoxyguanosine; O-Methylguanosine; Nelarabine (JAN/USAN); (2R,3R,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; (2R,3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; (3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; 2-(2-Amino-6-methoxy-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol; 2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; 2-Amino-6-methoxypurine arabinoside; 2-Amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine; 6'-O-Methylguanosine; 9-beta-D-Arabinofuranosyl-6-methoxy-9H-purin-2-amine; 9beta-D-Arabinofuranosyl-6-methoxy-9H-purin-2-amine

Indication

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[1]
T-cell acute lymphoblastic leukaemia	2A90.5	Approved	[2]
T-lymphoblastic lymphoma	N.A.	Approved	[2]

• Therapeutic Class: Anticancer Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  L01BB07: Nelarabine
  L01BB: Purine analogues
  L01B: ANTIMETABOLITES
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 297.27
  Logarithm of the Partition Coefficient (xlogp); -0.7
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 81 mL/min/kg [4]
  Elimination: 6.6% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3 hours [4]
  Metabolism: The drug is metabolized via the adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.234 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.8% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 4.9 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [3]
• Chemical Identifiers:
  Formula: C11H15N5O5
  IUPAC Name: (2R,3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
  Canonical SMILES: COC1=NC(=NC2=C1N=CN2[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)O)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
  InChIKey: IXOXBSCIXZEQEQ-UHTZMRCNSA-N
• Cross-matching ID:
  PubChem CID: 3011155
  ChEBI ID: CHEMBL1201112
  CAS Number: 121032-29-9
  UNII: 60158CV180
  DrugBank ID: DB01280
  TTD ID: D0B8UJ
  INTEDE ID: DR1136
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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA synthesis (DNA synth)	TTUBNVO	NOUNIPROTAC	Binder	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Adenosine aminohydrolase (ADA) Main DME	DEDQHBV	ADA_HUMAN	Substrate	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Nelarabine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Nelarabine and Roflumilast.	Asthma [CA23]	[8]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Nelarabine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[9]
Teriflunomide	DMQ2FKJ	Major	Additive myelosuppressive effects by the combination of Nelarabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[10]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Nelarabine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[11]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Nelarabine and Denosumab.	Low bone mass disorder [FB83]	[12]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Nelarabine and Tecfidera.	Multiple sclerosis [8A40]	[13]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Nelarabine and Siponimod.	Multiple sclerosis [8A40]	[14]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Nelarabine and Fingolimod.	Multiple sclerosis [8A40]	[15]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Nelarabine and Ocrelizumab.	Multiple sclerosis [8A40]	[16]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Nelarabine and Ozanimod.	Multiple sclerosis [8A40]	[8]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Nelarabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[17]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Nelarabine and Canakinumab.	Rheumatoid arthritis [FA20]	[18]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Nelarabine and Rilonacept.	Rheumatoid arthritis [FA20]	[18]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Nelarabine and Golimumab.	Rheumatoid arthritis [FA20]	[19]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Nelarabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[20]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Nelarabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[14]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7090).
• [2] Nelarabine FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Nelarabine. Drugs. 2008;68(4):439-47.
• [7] Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia. Onco Targets Ther. 2009 Feb 18;2:219-28.
• [8] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [9] Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
• [10] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [11] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [12] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [13] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [14] Cerner Multum, Inc. "Australian Product Information.".
• [15] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [16] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [17] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [18] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [19] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
• [20] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]